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Population pharmacokinetic model of blood THC and its metabolites in chronic and occasional cannabis users and relationship with on‐site oral fluid testing

Abstract : To develop a population pharmacokinetic (PP) model of delta-9-tetrahydrocannabinol (THC) and its metabolites in blood and to determine the relationship between blood THC pharmacokinetics and results of on-site oral fluid (OF) testing in chronic (CC) and occasional (OC) cannabis users. Methods: Fifteen CC (1-2 joints/day) and 15 OC (1-2 joints/week) aged 18-34 years were included, genotyped for their CYP2C9 polymorphisms. Twelve measurements of blood THC, 11-OH-THC and THC-COOH were carried out during the 24-hour period after controlled cross-over random inhalation of placebo, 10 mg or 30 mg of THC. OF tests (DrugWipe® 5S) were performed up to 6 hours and then stopped after two successive negative results. The blood concentrations and their relationship to OF testing results were analysed using a PP approach with NON-MEM® and R. Results: A three-compartment model described the pharmacokinetics of THC, with zero-order absorption, and a two-compartment model the metabolites. The fraction of THC converted to 11-OH-THC was 0.27 and the fraction of 11-OH-THC to THC-COOH was 0.86. Smoking 30 mg of THC decreased the THC bioavailability to 0.68 compared to 10 mg. CC showed a 2.41 greater bioavailability than OC, leading to higher C max and AUC for the three compounds for the same dose. The best model describing the probability of a positive OF test included THC blood concentration and the group as covariate: for a similar THC blood concentration, a CC was less likely to be positive than an OC. Conclusion: OC are more likely to screen positive than CC for a similar blood concentration.
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Submitted on : Thursday, April 21, 2022 - 2:36:14 PM
Last modification on : Thursday, May 5, 2022 - 3:11:43 AM
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Jean Alvarez, Sarah Hartley, Isabelle Etting, Mégane Ribot, Nawal Derridj‐ait‐younes, et al.. Population pharmacokinetic model of blood THC and its metabolites in chronic and occasional cannabis users and relationship with on‐site oral fluid testing. British Journal of Clinical Pharmacology, Wiley, 2021, 87 (8), pp.3139 - 3149. ⟨10.1111/bcp.14724⟩. ⟨inserm-03648363⟩

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