An Experimental Study of Diazepam and Alprazolam Kinetics in Urine and Oral Fluid Following Single Oral Doses

Temte, Vidar; Kjeldstadli, Kari; Bruun, Lina Dorthea; Birdal, Morris; Bachs, Liliana; Karinen, Ritva; Middelkoop, Gerrit; Øiestad, Elisabeth Leere; Høiseth, Gudrun

doi:10.1093/jat/bky062

Cited by 10 publications

(6 citation statements)

References 24 publications

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“…Smith-Kielland et al [9] reported that the half-life of diazepam was 20-50 h and that of nordiazepam was 40-100 h. In contrast, in our study, the elimination half-lives of diazepam and nordiazepam in urine were 38.27-653.00 h and 75.91-1915.83 h, respectively. Furthermore, the longest detection period of diazepam varies significantly, with reported values ranging from 0 to 68 h [10,15], compared with 347.10 ± 43.30 h (ranging from 144.00 to 360 h) observed in this study. The longest detection period of nordiazepam varies from 1.50 to 252.00 h [10,13], compared with 354.90 ± 18.50 h (288.00-360 h) observed in this study, indicating a significant difference.…”

Section: Discussioncontrasting

confidence: 56%

“…Furthermore, the longest detection period of diazepam varies significantly, with reported values ranging from 0 to 68 h [10,15], compared with 347.10 ± 43.30 h (ranging from 144.00 to 360 h) observed in this study. The longest detection period of nordiazepam varies from 1.50 to 252.00 h [10,13], compared with 354.90 ± 18.50 h (288.00-360 h) observed in this study, indicating a significant difference.…”

Section: Discussioncontrasting

confidence: 56%

“…However, oxazepam could not be detected throughout the whole process, suggesting that oxazepam, in urine, might convert completely to OG. However, some studies have reported the presence of oxazepam in urine samples because of the difference in sample preparation, which hydrolyzes the OG in urine with β-glucuronidase to produce oxazepam [ 10 , 12 ]. Additionally, as mentioned in the introduction, oxazepam in urine has a much lower conversion rate to OG than temazepam to TG; thus, we speculated that both oxazepam and temazepam in urine might be conjugated completely with glucuronide, justifying the omission of temazepam as an analyte for drug monitoring purposes as well.…”

Section: Discussionmentioning

confidence: 99%

“…The models estimate that diazepam reached its peak concentration (2.38 ± 1.26 ng/mL) in urine at 1.93 h, and nordiazepam reached its peak concentration (1.17 ± 0.40 ng/mL) in urine at 100.21 h. Umezawa et al [ 13 ] administered a single 10 mg oral dose of diazepam to five healthy subjects aged 28–48 years and reported that diazepam and nordiazepam reached their peak concentrations (9.08 ± 3.24 ng/mL, 8.19 ± 1.30 ng/mL) at 1.5 and 12 h, respectively. In another study [ 10 ], 11 European patients (nine male and two female volunteers aged 20–35 years) received a 10 mg oral dose of diazepam. The T max of nordiazepam in urine was 11 h, but the parent compound, diazepam, could not be detected.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, because of the convenience and non-invasive nature of its collection, testing for diazepam abuse in urine is also required for multiple reasons, including legal and workplace policies [8]. Studies have reported a great value in urine levels of metabolites of diazepam due to their longer detection window [9][10][11][12][13][14], but these studies used different animals or studied urinary kinetics for a short period of time and in a small number of subjects. More importantly, published detection methods for diazepam in urine always involve hydrolysis of the glucuronide metabolites and focus on diazepam as well as on its active metabolites nordiazepam, temazepam, and oxazepam.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants

Wang

Ren

et al. 2022

Drugs R D

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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. ConclusionThe results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening.

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