Using Population Pharmacokinetic Modeling to Estimate Exposure to Δ9-Tetrahydrocannabinol in an Observational Study of Cannabis Smokers in Colorado

被引：4

作者：

Sempio, Cristina ^{[1
]}

Bidwell, L. Cinnamon ^{[2
,3
]}

Hutchison, Kent ^{[2
,3
]}

Huestis, Marilyn A. ^{[4
]}

Klawitter, Jost ^{[1
]}

Christians, Uwe ^{[1
]}

Henthorn, Thomas K. ^{[1
,5
]}

机构：

[1] Univ Colorado, Dept Anesthesiol, Sch Med, 12705 E Montview Blvd,Suite 200, Aurora, CO 80045 USA

[2] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 USA

[3] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[4] Huestis & Smith Toxicol LLC, Saverna Pk, MD USA

[5] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO 80045 USA

来源：

THERAPEUTIC DRUG MONITORING | 2021年 / 43卷 / 04期

基金：

美国国家卫生研究院;

关键词：

pharmacokinetics; cannabis; Delta; 9-tetrahydrocannabinol; TIMELINE FOLLOW-BACK; SELF-REPORTED USE; BLOOD CANNABINOIDS; PLASMA; THC; FREQUENT; BIOAVAILABILITY; VALIDATION;

D O I：

10.1097/FTD.0000000000000882

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Background: Self-report questionnaires, weighing products consumed, and Delta 9-tetrahydrocannabinol (THC) biomarkers are established techniques for estimating cannabis exposure. Population pharmacokinetic modeling of plasma THC and metabolite concentrations by incorporating self-reported and weighed products as covariates could improve estimates of THC exposure in regular cannabis users. Methods: In this naturalistic study, blood samples were obtained from 36 regular smokers of cannabis for analysis of THC and its 2 metabolites at 4 time points: recruitment and during an experimental mobile laboratory assessment that included 3 time points: before, immediately after, and 1 hour after ad libitum legal market flower use. These data were analyzed using an established model of population pharmacokinetics developed from laboratory-controlled cannabis administration data. Elimination and metabolite production clearances were estimated for each subject as well as their daily THC doses and the dose consumed during the ad libitum event. Results: A statistically significant correlation existed between the daily THC dose estimated by self-report questionnaire and population pharmacokinetic modeling (correlation coefficient = 0.79, P < 0.05) between the weighed cannabis smoked ad libitum and that estimated by population pharmacokinetic modeling (correlation coefficient = 0.71, P < 0.05). Conclusion: Inclusion of self-reported questionnaire data of THC consumption improved pharmacokinetic model-derived estimates based on measured THC and metabolite concentrations. In addition, the pharmacokinetic-derived dose estimates for the ad libitum smoking event underestimated the THC consumption compared with the weighed amount smoked. Thus, the subjects in this study, who smoked ad libitum and used cannabis products with high concentrations of THC, were less efficient (lower bioavailability) compared with computer-paced smokers of low potency, NIDA cannabis in a laboratory setting.

引用

页码：536 / 545

页数：10

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