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Tytuł pozycji:

Study on the Pharmacokinetics of Diazepam and Its Metabolites in Blood of Chinese People.

Tytuł :
Study on the Pharmacokinetics of Diazepam and Its Metabolites in Blood of Chinese People.
Autorzy :
Wang LL; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Ren XX; Institute of Forensic Science, Ministry of Public Security, Beijing, 100038, China.
He Y; Institute of Forensic Science, Ministry of Public Security, Beijing, 100038, China.
Cui GF; Institute of Forensic Science, Ministry of Public Security, Beijing, 100038, China.
Wei ZW; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Jia J; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Cao J; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Liu Y; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.
Cong B; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China.; Department of Forensic Medicine, Hebei Medical University, Shijiazhuang, 050017, China.
Niu Y; Department of Criminal, The Ministry of Public Security, Beijing, 100038, China. .
Yun KM; School of Forensic Medicine, Shanxi Medical University, Taiyuan, 030001, China. .
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Źródło :
European journal of drug metabolism and pharmacokinetics [Eur J Drug Metab Pharmacokinet] 2020 Aug; Vol. 45 (4), pp. 477-485.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: <2010- >: Paris : Springer France
Original Publication: Paris, Edifor.
MeSH Terms :
Diazepam/*pharmacokinetics
Hypnotics and Sedatives/*pharmacokinetics
Administration, Oral ; Adult ; Asian Continental Ancestry Group ; China ; Chromatography, High Pressure Liquid ; Diazepam/administration & dosage ; Diazepam/blood ; Female ; Humans ; Hypnotics and Sedatives/administration & dosage ; Hypnotics and Sedatives/blood ; Male ; Metabolic Detoxication, Phase I ; Metabolic Detoxication, Phase II ; Models, Biological ; Solid Phase Extraction ; Tandem Mass Spectrometry ; Young Adult
Grant Information :
450 NSFC (81172906); 000 NSFC (81172906); 1 United States CX CSRD VA; 960 National Key Technology R & D Program of China (2007BAK26B05 and 2012BAK02B02); 000 National Key Technology R & D Program of China (2007BAK26B05 and 2012BAK02B02); 300 National Science and Technology Special Project Work (SQ2015FYJ010051); 000 National Science and Technology Special Project Work (SQ2015FYJ010051); 1 United States CX CSRD VA
Substance Nomenclature :
0 (Hypnotics and Sedatives)
Q3JTX2Q7TU (Diazepam)
Entry Date(s) :
Date Created: 20200329 Date Completed: 20210420 Latest Revision: 20210420
Update Code :
20210421
DOI :
10.1007/s13318-020-00614-8
PMID :
32219697
Czasopismo naukowe
Background and Objectives: Driving under the influence of diazepam is increasing in China. The pharmacokinetics of diazepam and its metabolites, especially the glucuronide metabolites, are helpful in the identification of diazepam use by drivers. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites (nordazepam, oxazepam, oxazepam glucuronide and temazepam glucuronide) in the blood of Chinese people, and to provide basic data for identifying diazepam use and estimating the time of last diazepam ingestion.
Methods: A total of 28 participants (14 men, 14 women) were recruited and each person received 5 mg diazepam orally. Whole blood was collected at 0 h (pre-dose), and 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h, and at 2 days, 3 days, 6 days, 12 days, and 15 days post-dose. Analytes of interest were extracted via solid-phase extraction and analyzed by a liquid chromatography tandem mass spectrometry method operated in a positive multiple response monitoring mode. Pharmacokinetic parameters were analyzed by a pharmacokinetic software DAS according to the non-compartment model. The time of last diazepam use was estimated using the concentration ratios of diazepam to metabolites and metabolites to metabolites from controlled drug administration studies.
Results: The respective time of maximum concentration, the maximum concentration and the elimination half-life of diazepam were 1.04 ± 1.00 h, 87.37 ± 31.92 ng/mL and 129.07 ± 75.00 h; of nordazepam were 133.14 ± 109.63 h, 3.80 ± 1.75 ng/mL, and 229.73 ± 236.83 h; of oxazepam were 100.29 ± 87.16 h, 1.62 ± 2.64 ng/mL, and 382.86 ± 324.58 h; of temazepam glucuronide were 44.43 ± 55.41 h, 2.08 ± 0.88 ng/mL, and 130.53 ± 72.11 h; and of oxazepam glucuronide were 66.86 ± 56.33 h, 1.10 ± 0.41 ng/mL, and 240.66 ± 170.12 h. A good correlation model was obtained from the concentration ratio of diazepam to nordazepam and the time of diazepam use, and the prediction errors were less than 20%.
Conclusions: This study provides a sensitive method to identify diazepam ingestion by monitoring diazepam and its metabolites including glucuronides, as well as to infer the time following oral consumption.

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