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
; 87(8): 3139-3149, 2021 08.
Article
em En
| MEDLINE
| ID: mdl-33386756
ABSTRACT
AIMS:
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 NONMEM® 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 Cmax 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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cannabis
/
Alucinógenos
Tipo de estudo:
Clinical_trials
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article