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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.

Br J Clin Pharmacol. 2021 Jan 02;:

Authors: Alvarez JC, Hartley S, Etting I, Ribot M, Derridj-Ait-Younes N, Verstuyft C, Larabi IA, Simon N

Abstract
OBJECTIVE: 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 pharmacokinetic and results of on-site oral fluid (OF) testing in chronic (CC) and occasional (OC) cannabis users.
METHODS: 15 CC (1-2 joints/day) and 15 OC (1-2 joints/week) aged 18-34 y were included, genotyped for their CYP2C9 polymorphisms. Twelve measurements of blood THC, 11-OH-THC and THC-COOH were carried out during 24-h after controlled cross-over random inhalation of placebo, 10mg or 30mg of THC. OF tests (DrugWipe® 5S) were performed up to 6 hours and then stopped after 2 successive negative results. The blood concentrations and their relationship to OF testing results were analysed using a PP approach with NONMEM® and R.
RESULTS: a three-compartment model described the pharmacokinetic 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 30mg of THC decreased the THC bioavailability to 0.68 compared to 10mg. CC showed a 2.41 greater bioavailability than OC, leading to higher Cmax and AUC for the 3 compounds for the same dose. The best model describing the probability of a positive OF testing 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.

PMID: 33386756 [PubMed – as supplied by publisher]


Source: ncbi 2

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