Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants,Drugs in R&D

当前位置： X-MOL 学术 › Drugs R D › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants
Drugs in R&D ( IF 2.2 ) Pub Date : 2022-01-31 , DOI: 10.1007/s40268-021-00375-y
Le-le Wang _{1,

2} , Xin-Xin Ren ₃ , Yi He ₃ , Guan-Feng Cui ₃ , Jia-Jia Liu _{1,

2} , Juan Jia _{1,

2} , Jie Cao _{1,

2} , Yao Liu _{1,

3} , Bin Cong _{1,

4} , Zhi-Wen Wei _{1,

2} , Ke-Ming Yun _{1,

2}

Affiliation

Background

Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine.

Objective

This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants.

Methods

A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography–tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model.

Results

Urinary diazepam peaked at 2.38 ng/mL (C_max) and 1.93 h (T_max). The urinary metabolite nordiazepam peaked at 1.17 ng/mL and 100.21 h; temazepam glucuronide (TG) peaked at 145.61 ng/mL and 41.14 h; and oxazepam glucuronide (OG) peaked at 101.57 ng/mL and 165.86 h. The elimination half-life (t_½z) and clearance (CLz/F) for diazepam were 119.58 h and 65.77 L/h, respectively. The t_½z of the metabolites nordiazepam, TG, and OG was 310.58 h, 200.17 h, and 536.44 h, respectively. Finally, this study found that both diazepam and its main metabolites in urine were detectable for at least 15 days, although there were individual differences.