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Efficacy, Safety, and Population Pharmacokinetics of Eltrombopag in Children with Different Severities of Aplastic Anemia J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-18 Wei Zhang, Li‐Xian Chang, Bei‐Bei Zhao, Yi Zheng, Dan‐Dan Shan, Bo‐Hao Tang, Fan Yang, Yue Zhou, Guo‐Xiang Hao, Ya‐Hui Zhang, van den Anker John, Xiao‐Fan Zhu, Li Zhang, Wei Zhao
Eltrombopag was approved as a first‐line treatment for patients older than 2 years old with severe aplastic anemia (SAA). However, data on eltrombopag in children with different types of aplastic anemia (AA), especially non‐severe AA (NSAA), are limited. We performed a prospective, single‐arm, and observational study to investigate eltrombopag's efficacy, safety, and pharmacokinetics in children with
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Pharmacokinetics‐Based Pediatric Dose Evaluation and Optimization Using Saliva – A Case Study J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-18 Marion Anliker‐Ort, Frédérique Rodieux, Victoria C. Ziesenitz, Andrew Atkinson, Julia A. Bielicki, Thomas O. Erb, Nicolas Gürtler, Stefan Holland‐Cunz, Urs Duthaler, Deborah Rudin, Manuel Haschke, John van den Anker, Marc Pfister, Verena Gotta
Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off‐label in infants. Six plasma and 6 saliva
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Pediatric Extrapolation Approach for U.S. Food and Drug Administration Approval of Brexpiprazole in Patients Aged 13 to 17 Years with Schizophrenia J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-16 Huixia Zhang, Jie Liu, Vishnu Sharma, Luning Zhuang, Pamela Horn, Ramana Uppoor, Mehul Mehta, Hao Zhu
A pharmacokinetic (PK) bridging approach was successfully employed to support the dosing regimen and approval of brexpiprazole in pediatric patients aged 13‐17 years with schizophrenia. Brexpiprazole was approved in 2015 for the treatment of schizophrenia and the adjunctive treatment of major depressive disorder in adults based on efficacy and safety data from clinical trials. On January 13, 2020,
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Integrating Full Bayesian Inference and Student's t‐Distribution Method for Enhanced Outlier Handling in Caffeine Population Pharmacokinetics: Assessing Drug–Drug Interactions with Enasidenib in Relapsed or Refractory AML and MDS Patients J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-13 Yiming Cheng, Shengnan Du, Hongxiang Hu, Xiaomin Wang, Leon Carayannopoulos, Yan Li
As the first‐in‐class, selective, and potent inhibitor of the isocitrate dehydrogenase‐2 (IDH2) mutant protein, enasidenib was approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an IDH2 mutation. Known for its interactions with various cytochrome P450 (CYP) enzymes and transporters in vitro
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Pharmacokinetics and Tolerability of a Single Dose of Apraglutide, a Novel, Long‐Acting, Synthetic glucagon‐like peptide‐2 Analog With a Unique Pharmacologic Profile, in Individuals With Impaired Renal Function J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-11 Gérard Greig, Nader N Youssef, Federico Bolognani
Renal impairment is a common complication in patients with short bowel syndrome with intestinal failure (SBS‐IF). Glucagon‐like peptide‐2 analogs, such as apraglutide, have been developed as a treatment option for SBS‐IF. This study assessed the potential for apraglutide overexposure in individuals with severely impaired renal function versus healthy volunteers with normal renal function. In this phase
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Changing Trajectories of Alanine Aminotransferase and Risk of Antituberculosis Drug‐Induced Liver Injury in Chinese Patients: A Cohort Study J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-04 Xinyu Chen, Hongqiu Pan, Zhuolu Hao, Honggang Yi, Shaowen Tang
Antituberculosis drug‐induced liver injury (ATLI) is a major adverse effect during antituberculosis treatment. Early detection or prediction is essential to prevent ATLI in antituberculosis treatment patients. The purpose of this work is to explore the relationship between alanine aminotransferase (ALT) trajectories within 15 days of initial treatment and the risk of ATLI. Based on a historical cohort
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Reversal of Opioid‐Induced Respiratory Depression in Healthy Volunteers: Comparison of Intranasal Nalmefene and Intranasal Naloxone J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-04 Mark Ellison, Emily Hutton, Lynn Webster, Phil Skolnick
An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed
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Pharmacokinetic and Pharmacodynamic Modeling Analysis of Delpazolid (LCB01‐0371) in Adult Patients with Pulmonary Tuberculosis J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-04 Sang Min Lee, Seung Chan Choi, Kyung Ran Mun, Ji Young Seo, Young Lag Cho, Tae Sun Shim, Hyeong‐Seok Lim
Delpazolid (LCB01‐0371) is a novel oxazolidinone derivative with a good safety profile for treating gram‐positive pathogenic infections such as Mycobacterium abscessus, a highly pathogenic drug‐resistant Mycobacterium. In this study, we evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of delpazolid after 14 days of multiple oral administration, using data from adult patients with pulmonary
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Application of Model‐Informed Drug Development in Dose Selection and Optimization for siRNA Therapies J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-01 Ye Yuan, Liang Li, Justin Earp, Lian Ma, Venkatesh Atul Bhattaram, Vishnu Sharma, Alexander Tong, Yaning Wang, Jiang Liu, Hao Zhu
The application of model‐informed drug development (MIDD) has revolutionized drug development and regulatory decision making, transforming the process into one that is more efficient, effective, and patient centered. A critical application of MIDD is to facilitate dose selection and optimization, which play a pivotal role in improving efficacy, safety, and tolerability profiles of a candidate drug
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Breast Milk Excretion of Dinalbuphine Sebacate Injection Administered After Cesarean Section J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-03-01 Sung‐Ling Tang, Kai‐Yi Wang, Wen‐Kai Hsiao, Chi‐Kang Lin
Ensuring the safety of analgesics during lactation is crucial for women of childbearing potential. Available data regarding the transfer of nalbuphine for postoperative acute pain via breast milk are limited to the postmarketing experience. This lactation study aimed to assess nalbuphine and dinalbuphine sebacate concentrations in breast milk from lactating women with postoperative pain treated with
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Effect of Age, Comedications, and CYP3A4/5 Polymorphisms on Perampanel Exposure in Chinese Pediatric Patients With Epilepsy J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-21 Huijuan Wang, Junyan Wang, Bin Lin, Huifen Zhang, Yangyang Sun, Yuanyuan Wu, Weifeng Ye, Jing Miao
Perampanel (PER) is a new type of antiseizure medication used for partial or generalized seizures. However, the plasma concentration shows obvious individual variability in children. The present study aims to ascertain the effect of age, comedications, and cytochrome P450 (CYP) 3A4/5 polymorphisms on PER exposure in Chinese pediatric patients with epilepsy. Clinical data were retrospectively collected
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Mechanistic Modeling of Empagliflozin: Predicting Pharmacokinetics, Urinary Glucose Excretion, and Investigating Compensatory Role of SGLT1 in Renal Glucose Reabsorption J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-16 Xian Ping, Guopeng Wang, Dongmei Gao
The aim of this study was to use a combination of physiologically based pharmacokinetic (PBPK) modeling and urinary glucose excretion (UGE) modeling to predict the time profiles of pharmacokinetics (PK) and UGE for the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMP). Additionally, the study aims to explore the compensatory effect of SGLT1 in renal glucose reabsorption (RGR) when
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A Real‐World Pharmacovigilance Study of Ceftazidime/Avibactam: Data Mining of the Food and Drug Administration Adverse Event Reporting System Database J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-20 Haiping Yao, Yanyan Wang, Yan Peng, Zhixiong Huang, Guoping Gan, Zhu Wang
Ceftazidime/avibactam (CAZ/AVI) is a combination of a well‐known third‐generation, broad‐spectrum cephalosporin with a new beta‐lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially multidrug‐resistant Gram‐negative bacterial infections) by the Food and Drug Administration (FDA). The current study extensively assessed CAZ/AVI‐related adverse events
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Therapeutic Strategies for Idiopathic Pulmonary Fibrosis – Thriving Present and Promising Tomorrow J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-12 Nikita Gupta, Mitali Paryani, Snehal Patel, Aditi Bariya, Anshu Srivastava, Yashwant Pathak, Shital Butani
Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue, which leads to a decline in the normal functioning of the lungs. The pathophysiology of IPF has still not been completely elucidated, so current strategies are lagging behind with respect to improving the condition of patients with IPF
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Feasibility of Using Population Pharmacokinetics-Based Virtual Control Groups in Organ Impairment Studies J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-12 Islam R. Younis, Fan Wang, Ahmed A. Othman
This work aimed to assess the feasibility of using population pharmacokinetics (popPK) to generate virtual healthy control groups in organ impairment studies. Data from 11 organ impairment studies containing 18 organ impairment arms and 13 healthy control groups across 7 drugs were analyzed. Area under the concentration-time curve (AUC) and maximum concentration (Cmax) were calculated from popPK-simulated
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Neonatal Therapeutics: Time for a More Effective and Impactful Collaboration Between Neonatologists and Clinical Pharmacologists J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-14 John N. van den Anker
Carefully vetted dosing recommendations for the majority of drugs used in the neonatal intensive care unit are currently lacking, partly because they have not been submitted to the strict regulatory processes of drug licensing that are normal in adult medicine. The paucity of licensed drugs and, as a consequence, unavoidable off-label use of drugs in neonates is a worldwide issue of paramount concern
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Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-10 Scott R. Penzak, Marilyn Bulloch
β-Phenyl-γ-aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online
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Exposure-Response Relationships for Pralsetinib in Patients with RET-Altered Thyroid Cancer or RET Fusion-Positive Nonsmall Cell Lung Cancer J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-09 Nastya Kassir, David McDougall, Denison Kuruvilla, Sean Kim, Shaun Kumar, Ahmadur Rahman, Thorsten Ruf, Sravanthi Cheeti, Wendy Ankrom
Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. Pralsetinib received approval from the United States Food and Drug Administration for the treatment of patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC), and received accelerated approval for the treatment of patients with RET fusion-positive thyroid
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Effects of Prolonged Administration of Tenofovir Disoproxil Fumarate-Containing Antiviral Regimen on Renal Function in Low-Risk of Kidney Injury HIV Patients J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-07 Yuan Yuan, Shenghua He, Huanxia Liu, Yuanhong He, Ruifeng Zhou, Yuan Yao, Ke Yin, Chunrong Lyu
This study intended to investigate the impact of long-term tenofovir fumarate (TDF) antiviral regimen on renal function in human immunodeficiency virus (HIV)-infected patients with low-risk of kidney injury. The observational study involving 100 HIV-infected patients without underlying diseases who achieved virological suppression and immunological recovery after sustained antiviral regimen of TDF+
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Indomethacin Pharmacokinetics and Pharmacodynamics in Pregnancies With Preterm Labor: The Need for Dose-Ranging Trials J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-05 Stephen J. Balevic, Daniel Weiner, Christoph P. Hornik, Michael Cohen-Wolkowiez, Daniel Gonzalez, Xiaoming Wang, Meixiang Xu, Sherif Z. Abdel-Rahman, Erik Rytting
The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the plasma disposition of indomethacin in pregnant women with PTL, and relate indomethacin exposure to delayed delivery and maternal/neonatal safety.
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Atezolizumab Plus Bevacizumab Versus Lenvatinib for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-04 Jinpeng Lu, Xinyi Lin, Haiwen Teng, Yansong Zheng
Hepatocellular carcinoma (HCC) is often diagnosed in advanced stages. Following sorafenib, lenvatinib (LENV) has been approved as a first-line treatment option for unresectable HCC. In the past few years, at least 9 large-scale cohort studies have examined the efficacy and safety of LENV compared to atezolizumab plus bevacizumab (ATE/BEV) in unresectable HCC, but there is currently no direct meta-analysis
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Mechanistic Framework to Predict Maternal-Placental-Fetal Pharmacokinetics of Nifedipine Employing Physiologically Based Pharmacokinetic Modeling Approach J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-02 Marya Antônya Werdan Romão, Leonardo Pinto, Ricardo Carvalho Cavalli, Geraldo Duarte, Natália Valadares de Moraes, Khaled Abduljalil, Fernanda de Lima Moreira
Nifedipine is used for treating mild to severe hypertension and preventing preterm labor in pregnant women. Nevertheless, concerns about nifedipine fetal exposure and safety are always raised. The aim of this study was to develop and validate a maternal-placental-fetal nifedipine physiologically based pharmacokinetic (PBPK) model and apply the model to predict maternal, placental, and fetal exposure
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Statin Drug-Drug Interactions: Pharmacokinetic Basis of FDA Labeling Recommendations and Comparison Across Common Tertiary Clinical Resources J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-02-01 James Mease, Anuradha Ramamoorthy, Xinning Yang, Rajanikanth Madabushi, Elimika Pfuma Fletcher, Issam Zineh
Statins are widely prescribed and highly susceptible to pharmacokinetic (PK)-based drug–drug interactions (DDIs). To date, there has not been a comprehensive analysis of the basis upon which statin DDI recommendations in US Food and Drug Administration (FDA) prescribing information (PI) are derived. We have conducted such an analysis. We also assessed the degree of concordance of statin DDI recommendations
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Food-Drug Effects and Pediatric Drug Development Studies Submitted to the US Food and Drug Administration, 2012-2022 J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-01-31 Kayla R. Tunehag, Blessy George, Sherbet Samuels, Karen Vo, Vikram Arya, Gelareh Abulwerdi, Gilbert J. Burckart
Food effect (FE) studies characterize food-drug interactions that may alter the efficacy or safety of a drug, but these studies are not conducted in pediatric patients. Pediatric patients have substantial physiologic, anatomic, and dietary differences from adults, which may result in differences in their FE considerations. Therefore, the objective of this study was to identify oral drug products approved
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Population Pharmacokinetics of Nirsevimab in Preterm and Term Infants J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-01-31 Lindsay Clegg, Ed Freshwater, Amanda Leach, Tonya Villafana, Ulrika Wählby Hamrén
Nirsevimab, a monoclonal antibody with an extended half-life, is approved for the prevention of respiratory syncytial virus (RSV) disease in all infants in Canada, the EU, Great Britain, and the USA. A population pharmacokinetics (PK) model was built to describe the PK of nirsevimab in preterm and term infants, and to evaluate the influence of covariates, including body weight and age, in infants.
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2023 JCP Peer Reviewer List J. Clin. Pharmacol. (IF 2.9) Pub Date : 2024-01-31
The Editor-in-Chief and Associate Editors of The Journal of Clinical Pharmacology would like to acknowledge and thank our peer reviewers for their contribution to the journal. Below is a list of those individuals who reviewed for JCP in 2023. Claude Abdallah Ahmed Abulfathi Francis Achike Anupam Agarwal Homa Ahmadzia Mariam Ahmed Valentin al Jalali Suliman Al-Fayoumi Karel Allegaert Barbara Ameer Elham
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Cannabis Science and Therapeutics: An Overview for Clinicians J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-25 Leah Sera, Carrie Hempel-Sanderoff
Cannabis-based therapeutics have garnered increasing attention in recent years as patients seek alternative treatments for various medical conditions. This narrative review provides a comprehensive overview of the science behind the medical use of cannabis, focusing on the medical evidence for commonly treated conditions. In addition, the review addresses the practical considerations of using cannabis
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A Nonsystematic Review of the Features of Pharmacotherapy in the Elderly at the Stage of Taking Medications J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-21 Lyudmila Yermukhanova, Kerbez Kimatova, Rysty Nazarbayeva, Zhanar Dostanova, Gulshara Aimbetova
The human body is subservient to the age-related changes that affect not only the outer appearance but also organs and tissues. They also concern the processes of pharmacokinetics and dynamics. This means that the absorption, distribution, and metabolism of drugs used by an elderly patient will be slowed down. Therefore, it becomes necessary to prescribe a special dosing regimen for older people. An
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Pharmacokinetics (PK) of Tiragolumab in First-in-Human Study in Patients with Mixed Solid Tumors (GO30103) J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-17 Elena Garralda, Do Youn Oh, Antoine Italiano, Philippe L. Bedard, Jean-Pierre Delord, Emiliano Calvo, Patricia LoRusso, Zev Wainberg, Andres Cervantes, Alejo Rodriguez-Vida, Colby S. Shemesh, Rucha Sane, Diana Mendus, Hao Ding, Robert Hendricks, Ray Meng, Byoung Chul Cho, Tae Won Kim, Benjamin Wu
Tiragolumab is a first-in-class, fully human IgG1/kappa anti-TIGIT monoclonal antibody that blocks the binding of TIGIT to CD155 (the poliovirus receptor). We summarize the pharmacokinetics (PK) data from the phase 1a/1b GO30103 study of Q3W (every 3 weeks) sequential dosing of tiragolumab (2, 8, 30, 100, 400, 600, or 1200 mg) followed by atezolizumab (1200 mg), Q4W (every 4 weeks) sequential dosing
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An Investigation in the Comparability of the Exposure and Recommended Dose of Selected Pfizer Drugs in East Asian Countries: Is Mutual Usage of Clinical Data Among East Asian Countries Feasible? J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-17 Diane D. Wang, Yanke Yu, Kei Fukuhara, Yuwang Liu, So-Young Park, Kourosh Parivar
The current regulatory path for new drug registration in East Asian countries has led to significant delay of the new medicines in these countries. A unified regulatory path and allowance of mutual usage of clinical data in East Asian countries would lead to cost saving in drug development and expedite the new drug registration in these countries. The objectives of the present analysis are to compare
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A Retrospective Analysis of Intravenous Insulin versus Insulin and Nebulized Albuterol for the Treatment of Hyperkalemia in the Emergency Department J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-15 Sara N. Roach, Meghan L. Fletcher, Preeyaporn Sarangarm
There is limited literature evaluating the use of nebulized albuterol in the management of hyperkalemia. The objective was to evaluate the efficacy of insulin alone compared with the addition of nebulized albuterol for the treatment of hyperkalemia. This is a retrospective, single-center evaluation of adult patients with hyperkalemia attending the Emergency Department of a large urban academic medical
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Clinical Analysis of Immune-Related Adverse Events in 78 Patients with Advanced Metastatic Lung Cancer Treated with Immune Checkpoint Inhibitors J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-14 Yan Wang, Change Jin, Shengguo Liu, Chenhui Li, Jinfan Qiu, Zhengqiang He, Di Wu
To analyze the clinical features and possible risk factors of immune-related adverse events (irAEs) in patients with advanced metastatic lung cancer treated with immune checkpoint inhibitors. The clinical data of 78 patients with advanced metastatic lung cancer who were treated with immune checkpoint inhibitors in the Respiratory Department of Shenzhen People's Hospital from January 2020 to November
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Demographic Diversity of Clinical Trials for Therapeutic Drug Products: A Systematic Review of Recently Published Articles, 2017-2022 J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-14 Wambui Chege, Atasi Poddar, Marsha E. Samson, Cecilia Almeida, Rihana Miller, Dina Raafat, Tala Fakhouri, Mathilda Fienkeng, Stephanie O. Omokaro, Victor Crentsil
The US Food and Drug Administration (FDA) encourages the use of enrollment practices that will lead to clinical trials that reflect the population most likely to use the therapeutic product (drug or biologic), if approved. In doing so, the benefit-risk profile of the product may be assessed more completely and offer patients and their health care providers a better understanding of the drug profile
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Pharmacokinetics of Tacrolimus in Pregnant Solid-Organ Transplant Recipients: A Retrospective Study J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-12 Jorn Versluis, Arno R. Bourgonje, Daan J. Touw, Jildau R. Meinderts, Jelmer R. Prins, Margriet F. C. de Jong, Paola Mian
Data on the pharmacokinetics of tacrolimus during pregnancy are limited. Therefore, the aim of this retrospective study was to characterize the whole-blood pharmacokinetics of tacrolimus throughout pregnancy. In this single-center retrospective cohort study, whole-blood tacrolimus trough concentrations corrected for the dose (concentration-to-dose [C/D] ratios) were compared before, monthly during
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External Evaluation of Population Pharmacokinetic Models for High-Dose Methotrexate in Adult Patients with Hematological Tumors J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-11 Shengyang Chen, Lifeng Huang, Weikun Huang, You Zheng, Li Shen, Maobai Liu, Wansheng Chen, Xuemei Wu
Currently, numerous population pharmacokinetic (popPK) models for methotrexate (MTX) have been published for estimating PK parameters and variability. However, it is unclear whether the accuracy of these models is sufficient for clinical application. The aim of this study is to evaluate published models and assess their predictive performance according to the standards of scientific research. A total
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Effects of CYP2D6 *10 and *41 Variants in Healthy Chinese Men on the Pharmacokinetics of Dapoxetine J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-07 Zhipeng Wang, Yuan Gao, Xingfang Ji, Tong Wu, Libin Pu, Wen Qiu
Dapoxetine is a selective serotonin reuptake inhibitor (SSRI) used to treat premature ejaculation (PE), and is mainly metabolized by CYP2D6, CYP3A4, and flavin-containing monooxygenase 1. The purpose of the study was to evaluate the effect of CYP2D6 polymorphism on the pharmacokinetics of dapoxetine in healthy Chinese men. Thirty-nine subjects who received a single oral dose of 30 mg dapoxetine hydrochloride
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Prescription of Oral Contraceptives by Licensed Pharmacists in the USA J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-04 Aarti Sawant-Basak, Priyanka Ingle-Jadhav
Conflicts of Interest The authors declare no conflict of interest.
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An Updated Comprehensive Pharmacovigilance Study of Drug-Induced Thrombocytopenia Based on FDA Adverse Event Reporting System Data J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-12-01 Li Kunyu, Shi Shuping, Su Chang, Cao Yiyue, Xiong Qinyu, Zhang Ting, Wu Bin
Drug-induced thrombocytopenia (DIT) deserves both clinical and research attention for the serious clinical consequences and high prevalence of the condition. The current study aimed to perform a comprehensive pharmacovigilance analysis of DIT reported in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, with a particular focus on drugs associated with thrombocytopenia
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Infliximab Concentrations in Participants with Moderate to Severe COVID-19 J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-30 Stephen J. Balevic, Dima Dandachi, Danielle Dixon, Richard M.W. Hoetelmans, Sam Bozzette, Matthew W. McCarthy
Infliximab is a chimeric monoclonal antibody that binds to soluble and membrane-bound tumor necrosis factor-alpha (TNF-α). TNF-α is a proinflammatory cytokine implicated in severe coronavirus disease 2019 (COVID-19), driving acute respiratory distress syndrome.1, 2 Accordingly, infliximab was investigated as a potential therapeutic agent for patients with moderate to severe COVID-19 in ACTIV-1, a randomized
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The Vision for Expanding the Visibility of the Journal of Clinical Pharmacology: Meet the New Editor-in-Chief and the 3 New Associate Editors! J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-28 John N. van den Anker, Vikram Arya, Catherijne A. J. Knibbe, Honghui Zhou
Seven remarkable Editors-in-Chief (EICs) have been at the helm of The Journal of Clinical Pharmacology during the last 63 years: Drs McKeen Cattell, Donald K. Adler, John C. Somberg, Deborah L. Keefe, Lisa L. von Moltke, Daniel S. Sitar, and Joseph S. Bertino Jr. These EICs have worked diligently to make the journal into the high-quality, well-respected publication it is today. We especially want to
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Physiologically Based Pharmacokinetic Modeling for Maribavir to Inform Dosing in Drug-Drug Interaction Scenarios with CYP3A4 Inducers and Inhibitors J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-27 Grace Chen, Kefeng Sun, Ingrid Michon, Zoe Barter, Sibylle Neuhoff, Lipika Ghosh, Katarina Ilic, Ivy H. Song
Maribavir, an orally available antiviral agent, has been approved in multiple countries for the treatment of patients with refractory post-transplant cytomegalovirus (CMV) infection and/or disease. Maribavir is primarily metabolized by CYP3A4; coadministration with CYP3A4 inducers and inhibitors may significantly alter maribavir exposure, thereby affecting its efficacy and safety. The effect of CYP3A4
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Pharmacokinetic and Pharmacodynamic Analysis of Acetaminophen and Ibuprofen Dual Therapy for Patent Ductus Arteriosus Closure in Preterm Neonates at Less Than 29 Weeks of Gestation J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-27 Mohammed Almoslem, Sanket D. Shah, Valvanera Vozmediano, Serge Guzy, Sarah Kim, Mark L. Hudak, Stephan Schmidt
Patent ductus arteriosus (PDA) is a blood vessel that critically supports fetal circulation. The ductus naturally closes within a few days after birth. However, it can stay open in premature neonates for an extended period of time, which is associated with increased mortality and various co-morbidities. Ibuprofen and indomethacin are currently the only 2 drugs approved for inducing PDA closure, but
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Application of a Precision-Dosing Model to a Real-World Cohort of Patients on Infliximab Maintenance Therapy: Drug Usage and Cost Analysis J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-15 Anke L. Nguyen, Peter R. Gibson, Richard N. Upton, Diane R. Mould, Miles P. Sparrow
Precision-dosing models forecast infliximab doses to achieve targeted trough concentrations in patients with inflammatory bowel disease (IBD). These models have shown to reduce nonresponse and improve patient outcomes. We compared infliximab doses determined by iDOSE precision dosing with standard dosing, and the associated drug costs, in patients with IBD. In this retrospective study, patients with
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Griseofulvin-Induced Red and Hot Ears J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-13 Anand Mannu, Abhinav Kumar Verma, Biju Vasudevan, Pankaj Das, Lekshmipriya Krishnan
Dear Editor, Griseofulvin is a natural product, first isolated in 1939 from Penicillium griseofulvum and was first commercially introduced in 1959. It is a polyketide that is derived from acetyl and malonyl coenzyme A precursor molecules to form dehydrogriseofulvin.1 It inhibits microtubule assembly, affects the formation of the mitotic spindle, and finally inhibits mitosis in dermatophytes.2 Griseofulvin
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Population Pharmacokinetics of Caffeine in Neonates with Congenital Heart Disease and Associations with Acute Kidney Injury J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-07 Elizabeth J. Thompson, Kanecia O. Zimmerman, Daniel Gonzalez, Henry P. Foote, Sangah Park, Kevin D. Hill, Jillian H. Hurst, Chi D. Hornik, Reid C. Chamberlain, Rasheed A. Gbadegesin, Christoph P. Hornik
Cardiac surgery-associated acute kidney injury (CS-AKI) occurs in approximately 65% of neonates undergoing cardiac surgery on cardiopulmonary bypass and contributes to morbidity and mortality. Caffeine may reduce CS-AKI by counteracting adenosine receptor upregulation after bypass, but pharmacokinetics (PK) in this population are unknown. The goal of our analysis is to address knowledge gaps in age-
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Child and Adolescent Bariatric Surgery in an Urban Tertiary Center: Special Anesthetic Considerations for Obesity. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Janelle D Vaughns,Reaundra McCullough-Roach,Elaine F Williams,Evan P Nadler
Children and adolescents with obesity who present for weight loss surgery are a unique subset of patients. A thorough understanding of the perioperative needs of these individuals is essential to avoid deleterious complications. This review illustrates the necessity for specialized care, including the continued need of specified drug dosing and a systematic approach in the management of the pediatric
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The Importance of Assessing Drug Pharmacokinetics and Pharmacodynamics in the Obese Population During Drug Development. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Kenneth T Moore,Peter N Zannikos,Joanna C Masters,Stefan Willmann,Jinshan Shen,Charles Frost
Obesity remains a US national health crisis and a growing concern worldwide. Concerningly, individuals who are obese are at an increased risk for comorbid diseases that include, but are not limited to, hypertension, diabetes, cardiovascular disease, and cancer. Beyond the risk for developing these conditions, obesity may also impact the pharmacological activity of the therapies being used to treat
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Clinical Consequences of Altered Drug Disposition in Obesity: Call for Change. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Christopher D Bruno,David J Greenblatt,Jerold S Harmatz,Christina R Chow
Obesity is a serious condition with many known comorbid conditions and other health risks. Despite the rising global rates of obesity, drug disposition in this population is typically understudied, which results in limited information guiding the use of drugs in patients with obesity. Presently, dosing adjustments for patients with obesity typically focus on addressing altered drug clearance with body
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Estimation of Absolute and Relative Body Fat Content Using Noninvasive Surrogates: Can DXA Be Bypassed? J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 David J Greenblatt,Christopher D Bruno,Jerold S Harmatz,Bess Dawson-Hughes,Qingchen Zhang,Chunhui Li,Christina R Chow
Dual-energy x-ray absorptiometry (DXA) scanning is used for objective determination of body composition, but instrumentation is expensive and not generally available in customary clinical practice. Anthropometric surrogates are often substituted as anticipated correlates of absolute and relative body fat content in the clinical management of obesity and its associated medical risks. DXA and anthropometric
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Inclusion of Subjects who are Obese in Drug Development: Current Status and Opportunities. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Jayabharathi Vaidyanathan,Elimika Pfuma Fletcher,Anuradha Ramamoorthy,Rajanikanth Madabushi,Gilbert J Burckart
The prevalence of obesity has grown tremendously in recent years and this population has an increased risk of disease comorbidities. The presence of disease comorbidities requires treatment interventions and proper dosing guidelines. However, drug development programs often do not have adequate representation of individuals who are obese in clinical trials, leaving gaps in the understanding of treatment
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Obesity Considerations in Pediatric Drug Development, 2016-2021. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Sherbet Samuels,Varsha Bhatt-Mehta,Kyunghun Park,Gilbert J Burckart
Pediatric obesity is a global public health concern. Obesity-related physiological changes may affect the pharmacokinetics of drugs and lead to therapeutic failure or toxicities. An earlier review of pediatric drug development programs from 2007 to 2016 found that, of 89 programs listing obesity-related terms, only 4 (4%) products described pharmacokinetic changes associated with obesity. This review
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Effect of Obesity on the Pharmacokinetics and Pharmacodynamics of Anticancer Agents. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 William C Zamboni,Rosane Charlab,Gilbert J Burckart,Clinton F Stewart
An objective of the Precision Medicine Initiative, launched in 2015 by the US Food and Drug Administration and National Institutes of Health, is to optimize and individualize dosing of drugs, especially anticancer agents, with high pharmacokinetic and pharmacodynamic variability. The American Society of Clinical Oncology recently reported that 40% of obese patients receive insufficient chemotherapy
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Is There a Need for a Dedicated Pharmacokinetic Trial for a Drug in Obese Populations? A Drug Prioritization Decision Tree Framework. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Brooke Langevin,Jogarao V S Gobburu,Mathangi Gopalakrishnan
Obesity is a growing global health concern associated with high comorbidity rates, leading to an increasing number of patients who are obese requiring medication. However, clinical trials often exclude or under-represent individuals who are obese, creating the need for a methodology to adjust labeling to ensure safe and effective dosing for all patients. To address this, we developed a 2-part decision
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Dosing Strategy of Immunoglobulin (IgG) Replacement Therapies in Obese and Overweight Patients with Primary Immunodeficiency Diseases (PIDDs): A Meta-Analysis of Clinical Trials. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Tingting Zhou,Million A Tegenge,Basil Golding,John Scott
The current dosing strategy of immune globulin products for the treatment of primary immunodeficiency diseases (PIDDs) in the USA is based on total body weight (BW). The aim of our study was to assess the relationship between dose and trough level, and to determine whether an alternative dosing strategy should be considered for patients who are overweight or obese. We analyzed data in a total of 533
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Model-Informed Approaches to Support Drug Development for Patients With Obesity: A Regulatory Perspective. J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Xiaolei Pan,Li Wang,Jiang Liu,Justin C Earp,Yuching Yang,Jingyu Yu,Fang Li,Youwei Bi,Atul Bhattaram,Hao Zhu
Obesity, which is defined as having a body mass index of 30 kg/m2 or greater, has been recognized as a serious health problem that increases the risk of many comorbidities (eg, heart disease, stroke, and diabetes) and mortality. The high prevalence of individuals who are classified as obese calls for additional considerations in clinical trial design. Nevertheless, gaining a comprehensive understanding
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Physiologically Based Pharmacokinetic Modeling of Nilotinib for Drug-Drug Interactions, Pediatric Patients, and Pregnancy and Lactation J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Xiaomei I. Liu, Ruby Leong, Gilbert J. Burckart, André Dallmann
Nilotinib is a second-generation BCR-ABL tyrosine kinase inhibitor for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia in both adult and pediatric patients. The pharmacokinetics (PK) of nilotinib in specific populations such as pregnant and lactating people remain poorly understood. Therefore, the objectives of the current study were to develop a physiologically based pharmacokinetic
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Population Pharmacokinetics of Ozoralizumab in Patients with Rheumatoid Arthritis J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Tsutomu Takeuchi, Yukihiro Chino, Yoko Mano, Masafumi Kawanishi, Yuri Sato, Saeko Uchida, Yoshiya Tanaka
Ozoralizumab is a bispecific NANOBODY compound that binds tumor necrosis factor alpha (TNFα) and human serum albumin. Ozoralizumab inhibits the TNFα physiological activity while maintaining long-term plasma retention owing to its human serum albumin–binding ability. A population pharmacokinetic (PK) model was developed using data from 494 Japanese patients with rheumatoid arthritis in Phase II/III
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Hypokalemia and Hyponatremia in Adult Patients Receiving Voriconazole Therapeutic Drug Monitoring J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-11-01 Lin Cheng, Zhirui Liu, Mingjie Yu, Ling Lin, Lirong Xiong, Qing Dai
Hypokalemia and hyponatremia are common but easily ignored adverse events in treatment with voriconazole (VCZ) that can lead to serious consequences. We intend to investigate the incidence of VCZ-induced hypokalemia and hyponatremia and their risk factors based on real-world data. A prospective study was conducted. A total of 272 patients with 414 VCZ plasma trough concentrations (C0) and VCZ N-oxide
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Five-Year Outcomes of Continuous Treatment with Zoledronic Acid Versus Denosumab in Older Men with High Fracture Risk: Risk Factor Analysis of Bone Density Improvement and Incidence of New Fracture J. Clin. Pharmacol. (IF 2.9) Pub Date : 2023-10-28 Tong-Che Wu, Yun-Jui Tsou, Wen-Tien Wu, Ru-Ping Lee, Jen-Hung Wang, Kuang-Ting Yeh
Denosumab and zoledronic acid are both effective and easily administrable injectable anti-osteoporotic medications for postmenopausal women. This study investigated the treatment efficacy of these agents in older male patients with low a bone mass and history of fragility fracture. A cohort of 175 male patients receiving continuous zoledronic acid treatment and a cohort of 366 male patients receiving