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Thank you to reviewers Xenobiotica (IF 1.8) Pub Date : 2024-03-18
Published in Xenobiotica: the fate of foreign compounds in biological systems (Vol. 54, No. 1, 2024)
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Effects of Pharmacogenetics on Pharmacokinetics and Toxicity of Doxorubicin in Egyptian Breast Cancer Patients Xenobiotica (IF 1.8) Pub Date : 2024-03-16 N.F. Ebaid, K.S. Abdelkawy, M.A. Shehata, H.F. Salem, G. Magdy, R.R.S. Hussein, F. Elbarbry
1. This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients ...
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Assessment of Cytochrome P450 Induction in Canine Intestinal Organoid Models Xenobiotica (IF 1.8) Pub Date : 2024-03-05 Itsuma Nagao, Meg Nakazawa, Takashi Goyama, Michael H. Court, Yoko M. Ambrosini
Published in Xenobiotica: the fate of foreign compounds in biological systems (Just accepted, 2024)
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Safflower Yellow for injection enhances anti-coagulation of warfarin in rats: Implications in pharmacodynamics and pharmacokinetics Xenobiotica (IF 1.8) Pub Date : 2024-03-06 Yan Liu, Jiahui Sun, Chunjuan Yang, Mengnan Qin, Shiwei Xu, Yue Zhao, Gaofeng Liu
This study investigated whether Safflower Yellow for injection (SYI) would affect the anticoagulation of warfarin in rats.Wistar male rats were divided into six groups randomly and administered wit...
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Reversible oxidation/reduction steps in the metabolic degradation of the glycerol side chain of the S1P1 modulator ponesimod Xenobiotica (IF 1.8) Pub Date : 2024-02-24 Alexander Treiber, Swen Seeland, Jérôme Segrestaa, Cyrille Lescop, Martin H. Bolli
1. Ponesimod is a selective modulator of the sphingosine 1-phosphate receptor 1 (S1P1) approved for the treatment of active relapsing forms of multiple sclerosis. The chemical structure of ponesimo...
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Rehmannioside A inhibits the activity of CYP3A4, 2C9 and 2D6 in vitro Xenobiotica (IF 1.8) Pub Date : 2024-02-22 Congrong Wang, Naixiang Zhou, Mingcui Li, Haixia Chen
1. To assess the effect of Rehmannioside A on CYP450s activity and to estimate its inhibitory properties.2. The effect of Rehmannioside A on the activity of major CYP450s in human liver microsomes ...
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The Effects of Genetic Polymorphism on Toxicity and Pharmacokinetics of Methotrexate in Egyptian Adult Patients with Leukaemia or Lymphoma Xenobiotica (IF 1.8) Pub Date : 2024-02-21 Khloud Shendy, Khaled Abdelkawy, Ahmed Amin Ali, Fathalla Belal, Mostafa Abdelhakiem, Galal Magdy, Nahla Anber, Fawzy Elbarbry
1. Polymorphisms in genes coding folate-metabolizing enzymes might alter the pharmacokinetics and sensitivity for methotrexate “MTX”.2. The aim of the study aimed to investigate the influence of MT...
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The Metabolism of the Orexin-1 Selective Receptor Antagonist Nivasorexant Xenobiotica (IF 1.8) Pub Date : 2024-02-15 Alexander Treiber, Swen Seeland, Belal Haschimi, Aude Weigel, Jodi T. Williams, Jerome Gabillet
1. Nivasorexant was the first orexin-1 selective receptor antagonist entering clinical development. Despite encouraging preclinical evidence in animal models, a proof-of-concept trial in binge eati...
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Development of a physiologically based pharmacokinetic model for levetiracetam in patients with renal impairment to guide dose adjustment based on steady-state peak/trough concentrations Xenobiotica (IF 1.8) Pub Date : 2024-02-12 Rongrong Wang, Tianlin Wang, Xueliang Han, Mengli Chen, Shu Li
1. Levetiracetam may cause acute renal failure and myoclonic encephalopathy at high plasma levels, particularly in patients with renal impairment. The aim of this study was to develop a physiologic...
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Sodium dodecylbenzene sulfonate (SDBS) present in detergents: action on the gills, skin, and blood of D. rerio fish Xenobiotica (IF 1.8) Pub Date : 2024-02-08 Eduardo LibanioReisSantos, Odaiza Silva, Jeffesson de Oliveira-Lima, Maria Izabel Camargo-Mathias
Sodium dodecylbenzene sulfonate (SDBS) is one of the surfactants used worldwide in detergents which, due to high residual discharges, has great potential to cause ecotoxicological impacts. Therefor...
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Utility of human cytochrome P450 inhibition data in the assessment of drug-induced liver injury Xenobiotica (IF 1.8) Pub Date : 2024-02-05 Shunnosuke Kaito, Jun-ichi Takeshita, Misaki Iwata, Takamitsu Sasaki, Takuomi Hosaka, Ryota Shizu, Kouichi Yoshinari
1. Drug-induced liver injury (DILI) is a major cause of drug development discontinuation and drug withdrawal from the market, but there are no golden standard methods for DILI risk evaluation. Sinc...
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High-throughput assay to simultaneously evaluate activation of CYP3A and the direct and time-dependent inhibition of CYP3A, CYP2C9, and CYP2D6 using liquid chromatography-tandem mass spectrometry Xenobiotica (IF 1.8) Pub Date : 2024-01-24 Yu Yumoto, Takuro Endo, Hiroshi Harada, Kaoru Kobayashi, Takeshi Nakabayashi, Yoshikazu Abe
In the early stages of drug discovery, adequate evaluation of the potential drug–drug interactions (DDIs) of drug candidates is important. Several CYP3A activators are known to lead to underestimat...
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Prediction of combination effect of quinidine on the pharmacokinetics of tipepidine using a physiologically based pharmacokinetic model Xenobiotica (IF 1.8) Pub Date : 2024-01-09 Shun Hayashi, Hiroko Kawaguchi, Takao Watanabe, Izuru Miyawaki, Tatsuki Fukami, Miki Nakajima
Tipepidine, an antitussive drug, has been reported to have central pharmacological effects and can be expected to be safely repositioned as treatment for psychiatric disorders. Since tipepidine req...
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Preclinical characterization of the absorption and disposition of the brain penetrant PI3K/mTOR inhibitor paxalisib and prediction of its pharmacokinetics and efficacy in human Xenobiotica (IF 1.8) Pub Date : 2024-01-10 Laurent Salphati, Jodie Pang, Bruno Alicke, Emile G. Plise, Jonathan Cheong, Allan Jaochico, Alan G. Olivero, Deepak Sampath, Susan Wong, Xiaolin Zhang
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. Available treatments have not markedly improved patient survival in the last twenty years. However, genomic investig...
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Meeting report of the 4th European Biotransformation Workshop Xenobiotica (IF 1.8) Pub Date : 2024-01-04 M. Walles, A. Pähler, E.M. Isin, Marie M. Ahlqvist
Challenges, strategies and new technologies in the field of biotransformation were presented and discussed at the fourth European Biotransformation Workshop which was held in collaboration with the...
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Effect of tubeimoside I on the activity of cytochrome P450 enzymes in human liver microsomes Xenobiotica (IF 1.8) Pub Date : 2024-01-03 Rui Wang, Kai Zheng, Yunjiao Liu, Shuxia Ji, Yaxin Tang, Jie Wang, Rong Jiang
This study assessed the effect of tubeimoside I on CYP1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4 to reveal the potential of tubeimoside I to induce drug-drug interaction.The evaluation of cytochro...
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Indirubin mediates adverse intestinal reactions in guinea pigs by downregulating the expression of AchE through AhR Xenobiotica (IF 1.8) Pub Date : 2024-01-02 Xiaoting Xu, Reham Taha, Chenghan Chu, Li Xiao, Tao Wang, Xinzhi Wang, Xin Huang, Zhenzhou Jiang, Lixin Sun
Indirubin is the main component of the traditional Chinese medicine Indigo naturalis (IN), a potent agonist of aryl hydrocarbon receptors (AhRs). In China, IN is used to treat psoriasis and ulcerat...
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Dose proportionality and bioavailability of quinoxaline-based JNK inhibitor after single oral and intravenous administration in rats Xenobiotica (IF 1.8) Pub Date : 2024-01-02 Galina A. Frelikh, Elena A. Yanovskaya, Alexander P. Lakeev, Galina A. Chernysheva, Vera I. Smolyakova, Anastasia R. Kovrizhina
The dose proportionality and bioavailability of the potential anti-inflammatory and neuroprotective JNK inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime (IQ-1) were evaluated by comparing pharmac...
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Synthesis and evaluation of indomethacin prodrugs with a diester structure that are metabolically activated by human carboxylesterases Xenobiotica (IF 1.8) Pub Date : 2023-12-29 Daisuke Takani, Masato Takahashi, Masakiyo Hosokawa
1. Carboxylesterase (CES) has been studied extensively, mostly with substrates in the monoester structures. We investigated the relationship between indomethacin diester prodrugs and metabolic act...
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Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies Xenobiotica (IF 1.8) Pub Date : 2023-12-26 Gobardhan Bal, Lakshmi Kanakaraj, Bibhash Chandra Mohanta
The pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxic...
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Simultaneous determination of four phytoecdysteroids by LC-MS/MS: application to a comparative pharmacokinetic study in normal and adjuvant arthritis rats after oral administration of C. officinalis Kuan phytoecdysteroids extract Xenobiotica (IF 1.8) Pub Date : 2023-12-26 Haiqiang Wang, Deqiang Yang, Shuang Jiang, Yixuan Ren, Lihong Wu, Zhenyue Wang, Haixue Kuang, Zhibin Wang
C. officinalis Kuan is the dry root of Cyathula officinalis Kuan. Clinically, it is used for fall and flutter injury, rheumatism and arthralgia. Phytoecdysteroids have significant anti-inflammatory...
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Effect of berberine on pharmacokinetics and pharmacodynamics of atorvastatin in hyperlipidemia rats Xenobiotica (IF 1.8) Pub Date : 2023-12-26 Fan Wu, Mingyu Cui, Siwen Wang, Chao Yu, Weihong Yin, Jiao Li, Xueying Yan
Atorvastatin, an effective lipid-lowering drug, could reduce the risks of morbidity and mortality of cardiovascular diseases. Patients with cardiovascular diseases often use atorvastatin along with...
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4,4’-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages Xenobiotica (IF 1.8) Pub Date : 2023-12-26 Chen-Chung Lin, Brandon F. Law, Justin M. Hettick
Occupational exposure to the most widely used monomeric diisocyanate (dNCO), 4,4’-methylene diphenyl diisocyanate (MDI), may lead to the development of occupational asthma (OA). Alveolar macrophage...
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Study on the transport and internalisation mechanism of dietary supplement nattokinase in the small intestine using animal and Caco-2 cell monolayer models Xenobiotica (IF 1.8) Pub Date : 2023-12-26 Huawei Feng, Chang Liu, Qingqing Liu, Jie Wang, Yingyue Zeng, Yue Sun, Man Zhang, Hui Zhang, Zhikui Liu, Jian Zhao, Hongsheng Liu
Maintaining proper blood flow is critical to promoting good health. Nattokinase is a serine protease from Bacillus subtilis that has significant in vitro thrombolytic activity, but its mechanism as...
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Novel application of PBBM to justify impact of faster dissolution on safety and pharmacokinetics – a case study and utility in regulatory justifications Xenobiotica (IF 1.8) Pub Date : 2023-12-19 Rajkumar Boddu, Sivacharan Kollipara, Adithya Karthik Bhattiprolu, Tausif Ahmed
Physiologically based biopharmaceutics modelling (PBBM) was recognised as potential approach for biopharmaceutics applications. However, PBBM to justify safety is an unexplored area.In this manusc...
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Population pharmacokinetics of mycophenolic acid and dose optimisation in adult Chinese kidney transplant recipients Xenobiotica (IF 1.8) Pub Date : 2023-12-19 Kaisaner Rexiti, Xuehui Jiang, Ying Kong, Xu Chen, Hong Liu, Hongwei Peng, Xiaohua Wei
1. This study aimed to establish a population pharmacokinetic (PPK) model of mycophenolic acid (MPA), quantify the effect of clinical factors and pharmacogenomics of MPA, and optimise the dosage fo...
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Pharmacokinetic evaluation of oxaliplatin combined with S-1 (SOX) chemotherapy in a rat model of colorectal cancer with acute kidney injury: predictive renal biomarkers for dose optimisation Xenobiotica (IF 1.8) Pub Date : 2023-12-19 Takumi Tanaka, Shinji Kobuchi, Yukako Ito, Toshiyuki Sakaeda
Dose adjustment based on renal function is essential in S-1, which contains the 5‑fluorouracil prodrug tegafur, and platinum-based agent oxaliplatin (SOX) combination chemotherapy for colorectal c...
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Tree shrew cytochrome P450 2E1 is a functional enzyme that metabolises chlorzoxazone and p-nitrophenol Xenobiotica (IF 1.8) Pub Date : 2023-12-19 Genki Ushirozako, Norie Murayama, Kyoko Tsukiyama-Kohara, Hiroshi Yamazaki, Yasuhiro Uno
Cytochromes P450 (CYPs or P450s) are important enzymes for drug metabolism. Tree shrews are non-primate animal species used in various fields of biomedical research, including infection (especiall...
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Chronic Toxoplasma infection affects gene expression of drug-metabolizing enzymes in mouse liver Xenobiotica (IF 1.8) Pub Date : 2023-12-19 Yasuhiro Uno, Shotaro Uehara, Genki Ushirozako, Tatsunori Masatani, Hiroshi Yamazaki
Toxoplasma gondii is an intracellular protozoan parasite causing toxoplasmosis, an infectious disease affecting warm-blooded vertebrates worldwide. Many drug-metabolizing enzymes are located in th...
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CYP-catalysed cycling of clozapine and clozapine-N-oxide promotes the generation of reactive oxygen species in vitro Xenobiotica (IF 1.8) Pub Date : 2023-12-22 Ellen Kingston, Malcolm Tingle, Brandi L. Bellissima, Nuala Helsby, Kathryn Burns
Clozapine is an effective atypical antipsychotic indicated for treatment-resistant schizophrenia, but is under-prescribed due to the risk of severe adverse drug reactions such as myocarditis.A mech...
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Effect of genetic polymorphisms on the pharmacokinetics of gefitinib in healthy Chinese volunteers Xenobiotica (IF 1.8) Pub Date : 2023-12-18 Ying-Rong Chen, Xiang Yu, Li-Min Xu, Jue Mei, Meng-Li Tian, Min Xu, Qiu-Yue Jin, Li-Bing Ye, Shui-Xin Yang
Gefitinib is the first-generation drug of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) metabolised by the cytochrome P450 and transported by P-glycoprotein (ABCB1) and br...
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Through a computer monitor darkly: artificial intelligence in absorption, distribution, metabolism and excretion science. Xenobiotica (IF 1.8) Pub Date : 2023-12-14 Dennis A Smith, Lucy Melanie Burton, Sophie Amanda
Artificial Intelligence (AI) is poised or has already begun to influence highly absorption, distribution, metabolism and excretion (ADME) science. It is not in the area expected, that of superior m...
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The history and future of population pharmacokinetic analysis in drug development Xenobiotica (IF 1.8) Pub Date : 2023-12-05 Nathan Teuscher
1. The analysis of pharmacokinetic data has been in a constant state of evolution since the introduction of the term pharmacokinetics. Early work focused on mechanistic understanding of the absorpt...
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Metabolite characterization of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS Xenobiotica (IF 1.8) Pub Date : 2023-12-04 Yali Yuan, Weiqiang Wang, Jing Luo, Chongzhuang Tang, Yuandong Zheng, Jinghua Yu, Honghong Xu, Mingshe Zhu, Taijun Hang, Hao Wang, Xingxing Diao
1. LN005 is a peptide-drug conjugate (PDC) targeting glucose-regulated protein 78 (GRP78), to treat several types of cancer, such as breast, colon, and prostate cancer.2. As a new drug modality, un...
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Evobrutinib pathway to its major metabolite M463-2 and insights from a biotransformation and DDI perspective Xenobiotica (IF 1.8) Pub Date : 2023-11-26 Holger Scheible, Hanno Schieferstein, Ralf Schmidt, Klaus Pusecker, Ulrike Gradhand, Sathej Gopalakrishnan, Khalid Iqbal, Jennifer Dong, Reinaldo Jones, Claudia Meli, Jayaprakasam Bolleddula, Martin Dyroff, Katrin Georgi
Evobrutinib is a highly selective, covalent, central nervous system-penetrant Bruton’s tyrosine kinase (BTK) inhibitor, currently in Phase III trials for the treatment of relapsing multiple scleros...
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N, N-dimethyltryptamine forms oxygenated metabolites via CYP2D6 - an in vitro investigation Xenobiotica (IF 1.8) Pub Date : 2023-11-26 Emma Eckernäs, Alicia Macan-Schönleben, Moa Andresen-Bergström, Sofia Birgersson, Kurt-Jürgen Hoffmann, Michael Ashton
N, N-dimethyltryptamine (DMT) is a psychedelic compound that has shown potential in the treatment of depression. Aside from the primary role of monoamine oxidase A (MAO-A) in DMT metabolism, the me...
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Empirical scaling factor for predicting human pharmacokinetic profiles of disproportionate metabolites using the Css–MRTpo method and chimeric mice with humanised livers Xenobiotica (IF 1.8) Pub Date : 2023-11-26 Hidetaka Kamimura, Shotaro Uehara, Nao Yoneda, Hiroshi Suemizu
Predicting plasma concentration–time profiles of disproportionate metabolites in humans is crucial for evaluating metabolites according to the Safety Testing guidelines. We evaluated Css–MRTpo, an ...
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The metabolite profiling of YR-1702 injection in human plasma, urine and feces by HPLC-Q-TOF-MS/MS Xenobiotica (IF 1.8) Pub Date : 2023-11-26 Yuxuan Fan, Yufeng Ni, Minlu Cheng, Wenjing Guo, Huaye Gao, WenHui Hu, Chang Shu, Li Ding
YR-1702, a hybrid μ/κ/δ receptor agonist, is modified from the traditional opioid analgesic dezocine. It had shown both excellent analgesic effect and lower addiction in phase I clinical trial in C...
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Hyperoside ameliorates cisplatin-induced acute kidney injury by regulating the expression and function of Oat1 Xenobiotica (IF 1.8) Pub Date : 2023-11-26 Wenjing Yuan, Shanshan Kou, Ying Ma, Yusi Qian, Xinyu Li, Yuanyuan Chai, Zhenzhou Jiang, Luyong Zhang, Lixin Sun, Xin Huang
Cisplatin is a widely used chemotherapeutic agent to treat solid tumours in clinics. However, cisplatin-induced acute kidney injury (AKI) limits its clinical application. This study investigated th...
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Investigation of pharmacokinetic properties of a PEGylated bilirubin nanoparticle in male Sprague-Dawley rats using liquid chromatography-quadrupole time-of-flight mass spectrometry Xenobiotica (IF 1.8) Pub Date : 2023-11-16 Seo-jin Park, Jeong-hyeon Lim, Jiyu Lee, Jeongmin Lee, Sangsoo Hwang, Hyunjin Kim, Seunghyun Jo, Duckhyang Shin, Sang Ho MA, Myung L. Kim, Young G. Shin
Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.An in vitro microsomal stability...
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Predicting routes of phase I and II metabolism based on quantum mechanics and machine learning Xenobiotica (IF 1.8) Pub Date : 2023-11-15 Mario Öeren, Peter A. Hunt, Charlotte E. Wharrick, Hamed Tabatabaei Ghomi, Matthew D. Segall
1. Unexpected metabolism could lead to the failure of many late-stage drug candidates or even the withdrawal of approved drugs. Thus, it is critical to predict and study the dominant routes of meta...
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Comparative study on ABCB1-dependent efflux of anthracyclines and their metabolites: consequences for cancer resistance Xenobiotica (IF 1.8) Pub Date : 2023-11-03 Kamil Piska, Paulina Koczurkiewicz-Adamczyk, Marek Jamrozik, Adam Bucki, Marcin Kołaczkowski, Elżbieta Pękala
1. ABCB1 (P-glycoprotein, MDR1) is one of the most important transporter involved in cancer multi-drug resistance. It also plays a significant role in cancer resistance against anthracyclines, an a...
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Evaluation of the non-linearity of NA808 in liver not reflected in plasma using a rat pharmacokinetic study and PBPK modelling Xenobiotica (IF 1.8) Pub Date : 2023-11-03 Mizuki Yamane, Kazuhisa Ozeki, Ken Okano, Toshiyuki Kudo, Kiyomi Ito
When NA808, a potent HCV replication inhibitor, was intravenously administered to rats, it was distributed to the liver. The AUC ratio in the liver of 20 mg/kg to 2 mg/kg was greater than the dose...
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Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla Xenobiotica (IF 1.8) Pub Date : 2023-11-03 Yiqing Guo, Huanhuan Lv, Jing Lv, Zenghong Jiang
The in vitro metabolism of hirsutine was determined using liver microsomes and human recombinant cytochrome P450 enzymes. Under the current conditions, a total of 14 phase I metabolites were tenta...
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Cytochrome P450 1A2 and 2C enzymes autoinduced by omeprazole in dog hepatocytes and human HepaRG and HepaSH cells are involved in omeprazole 5-hydroxylation and sulfoxidation Xenobiotica (IF 1.8) Pub Date : 2023-11-03 Yasuhiro Uno, Shotaro Uehara, Genki Ushirozako, Norie Murayama, Hiroshi Suemizu, Hiroshi Yamazaki
The induction assay for the cytochromes P450 (P450s) is an important tool in drug discovery and development. The inductions of dog P450 1A2 and 3A12 by omeprazole and rifampicin were functionally ...
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Preclinical pharmacokinetic exploration of a novel osteoporotic quinazolinone-benzopyran-indole hybrid (S019-0385) using LC-MS/MS Xenobiotica (IF 1.8) Pub Date : 2023-11-03 Mukesh Kumar, Mridula Chauhan, Sarvesh Kumar Verma, Arpon Biswas, Alisha Ansari, Anjali Mishra, Sachin Nashik Sanap, Amol Chhatrapati Bisen, Koneni V. Sashidhara, Rabi Sankar Bhatta
1. The current investigation was to develop and validate the LC-MS/MS method in order to analyse the various pharmacokinetic parameters of S019-0385. A sensitive, selective, and robust LC-MS/MS app...
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Two curcumin analogs inhibited the function and protein expression of breast cancer resistance protein: in vitro and in vivo studies Xenobiotica (IF 1.8) Pub Date : 2023-10-05 Chung-Ping Yu, Yi-Ru Wang, Yu-Chi Hou, Min-Tsang Hsieh, Pei-Ying Li, Sheng-Chu Kuo, Shiuan-Pey Lin
1. Two curcumin analogs, (1E,6E)-1,7-bis(3,5-diethyl-4-hydroxyphenyl)hepta-1,6-diene-3,5- dione (N17) and its prodrug ((1E,6E)-3,5-dioxohepta-1,6-diene-1,7-diyl)bis(2,6-diethyl-4,1- phenylene)bis(3...
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Impact of tectoridin on the pharmacokinetics of florfenicol via targeting cytochrome P450 and P-glycoprotein of rats Xenobiotica (IF 1.8) Pub Date : 2023-10-05 Min Zhang, Bin Wang, Xu-ting Li, Qin Yin, Ge Liang, Si-cong Li
Belamcanda chinensis (L.) DC, commonly used with florfenicol in Chinese veterinary clinics for respiratory tract infections, contains the major effective isoflavone, tectoridin (TEC). This study ai...
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Pharmacokinetics of the novel 5-HT4 receptor agonist, DA-6886, in dogs Xenobiotica (IF 1.8) Pub Date : 2023-10-05 Dae Young Lee, Hee Eun Kang
The pharmacokinetics of a new 5-hydroxytryptamine receptor 4 agonist, DA-6886, intended for the treatment of constipation-predominant irritable bowel syndrome, were evaluated in beagle dogs followi...
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A physiologically-based pharmacokinetic/pharmacodynamic (PBPK/PD) model for the insecticide dimethoate Xenobiotica (IF 1.8) Pub Date : 2023-09-14 Richard Reiss, Anne Loccisano, Andrew Deines, Myoungwoo Kim, Gopinath Nallani, Appavu Chandrasekaran, Paul Whatling
1. Dimethoate is an organophosphate insecticide that is converted in vivo to omethoate, the active toxic moiety. Omethoate inhibits acetylcholinesterase (AChE) in the brain and red blood cells (RBC...
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Danazol increases the oral bioavailability of midazolam by inactivation of hepatic and intestinal CYP3A in rats Xenobiotica (IF 1.8) Pub Date : 2023-09-05 Shuhei Fukuno, Katsuhito Nagai, Akemi Kurotobi, Yuki Sahori, Ryo Nakagawa, Rena Nomura, Takuya Ito, Hiroki Konishi
Danazol (DNZ) is a synthetic androgen derivative used for the treatment of intractable hematological disorders. In this study, we investigated the effects of DNZ on CYP3A activity in hepatic and sm...
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Physiologically based pharmacokinetic modelling to predict drug–drug interactions for encorafenib. Part I. Model building, validation, and prospective predictions with enzyme inhibitors, inducers, and transporter inhibitors Xenobiotica (IF 1.8) Pub Date : 2023-09-04 Sivacharan Kollipara, Tausif Ahmed, Sivadasu Praveen
Encorafenib, a potent BRAF kinase inhibitor undergoes significant metabolism by CYP3A4 (83%) and CYP2C19 (16%) and also a substrate of P-glycoprotein (P-gp). Because of this, encorafenib possesses ...
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Physiologically based pharmacokinetic modeling (PBPK) to predict drug-drug interactions for encorafenib. Part II. Prospective predictions in hepatic and renal impaired populations with clinical inhibitors and inducers Xenobiotica (IF 1.8) Pub Date : 2023-08-29 Sivacharan Kollipara, Tausif Ahmed, Sivadasu Praveen
Encorafenib, a potent BRAF kinase inhibitor gets significantly metabolised by CYP3A4 (83%) and CYP2C19 (16%) and is a substrate for P-glycoprotein (P-gp). Due to significant metabolism by CYP3A4, e...
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The influence of temperature on the metabolic activity of CYP2C9, CYP2C19, and CYP3A4 genetic variants in vitro Xenobiotica (IF 1.8) Pub Date : 2023-08-23 Michiaki Kojima, Kanami Machida, Sumie Cho, Daichi Watanabe, Hiroyuki Seki, Miyuki Shimoji, Ayuko Imaoka, Hiroshi Yamazaki, F. Peter Guengerich, Katsunori Nakamura, Koujirou Yamamoto, Takeshi Akiyoshi, Hisakazu Ohtani
1. Temperature is considered to affect the activity of drug-metabolizing enzymes; however, no previous studies have compared temperature dependency among cytochrome P450 genetic variants. This stud...
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Metabolic exhaustion and casein kinase 1α drive deguelin-induced premature red blood cell death Xenobiotica (IF 1.8) Pub Date : 2023-08-21 Mohammad A. Alfhili, Jawaher Alsughayyir
1. Deguelin (DGN), a retinoid isolated from many plants, exhibits a potent anticancer activity against a wide spectrum of tumour cells. There is a dearth of evidence, however, regarding the toxicit...
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Absorption, distribution, metabolism and excretion of 14C-vatiquinone in rats, dogs, and human subjects Xenobiotica (IF 1.8) Pub Date : 2023-08-18 Jiyuan Ma, Lucy Lee, Bert Yao, Peter Giannousis, Martin Thoolen, Qing Ye, Lee Golden, Matthew Klein, Ronald Kong
Vatiquinone is a potent inhibitor of 15-lipoxygenase and is in clinical development for the treatment of mitochondrial diseases and other disorders characterised by high levels of oxidative stress ...
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Toxicokinetic and mass balance of morpholine in rats Xenobiotica (IF 1.8) Pub Date : 2023-08-17 Aleksandra Piotrowski, Saïd Kinani, Fabrice Nesslany, Nicolas Aubert, Sylvaine Ronga, Magali Boize, Salma Achawi, Pierre-André Cabanes
Morpholine (MOR) has a broad spectrum of use and represents high risk of human exposure. Ingested MOR can undergo endogenous N-nitrosation in the presence of nitrosating agents forming N-nitrosomor...
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In Silico ADME/Tox Comes of Age: Twenty Years Later Xenobiotica (IF 1.8) Pub Date : 2023-08-04 Sean Ekins, Thomas R. Lane, Fabio Urbina, Ana C. Puhl
ABSTRACT In the early 2000s pharmaceutical drug discovery was beginning to use computational approaches for absorption, distribution, metabolism, excretion and toxicity (ADME/Tox, also known as ADMET) prediction. This emphasis on prediction was an effort to reduce the risk of later stage failures from ADME/Tox. Much has been written in the intervening twenty plus years and significant expenditure has
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Power of integrating PBPK with PBBM (PBPK-BM): a single model predicting food effect, gender impact, drug-drug interactions and bioequivalence in fasting & fed conditions Xenobiotica (IF 1.8) Pub Date : 2023-07-25 Rajkumar Boddu, Sivacharan Kollipara, Gautam Vijaywargi, Tausif Ahmed
Abstract Over the past few years, PBPK and PBBM modelling have proven their significance in drug development. PBPK modelling is traditionally used to predict drug-drug interactions, exposures in special populations whereas PBBM modelling is a part of PBPK modelling that is used for a range of biopharmaceutics applications. Because of these differences in utilities, often PBPK and PBBM models are developed
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Biochemical responses of the mussel Perna perna after exposure to environmental concentrations of the UV filter Benzophenone-3 Xenobiotica (IF 1.8) Pub Date : 2023-07-21 Gabriel S. Cruz, Juliana R. Moser, Miguel Saldaña-Serrano, Camila L. V. Bastolla, Daína Lima, Carlos H. A. M. Gomes, Micheli R. de Castro, Uclédia R. A. dos Santos, Gabriel S. Coutinho, Jacó J. Mattos, Maria R. F. Marques
Abstract Personal care products, such as UV filters, are frequently present in aquatic ecosystems, but studies on their impact on marine organisms are still scarce. Here we addressed the effects of benzophenone-3 (BP-3) on the antioxidant status of Perna perna mussels exposed to concentrations of 0.1 and 3 μg.L−1 for 72 h and 7 days. Glutathione peroxidase (GPx), glutathione reductase (GR), glutathione