Population pharmacokinetic modeling of plasma Δ9-tetrahydrocannabinol and an active and inactive metabolite following controlled smoked cannabis administration.
Br J Clin Pharmacol
; 86(3): 611-619, 2020 03.
Article
em En
| MEDLINE
| ID: mdl-31747464
ABSTRACT
AIMS:
Population pharmacokinetic models of Δ9-tetrahydrocannabinol (THC) have been developed for THC plasma and blood concentration data. Often, only the metabolites of THC are measurable when blood samples are obtained. Therefore, we performed a population pharmacokinetic analysis of THC, 11-OH-THC and THCCOOH plasma concentration data from a Phase I clinical trial of THC smoking.METHODS:
Frequently obtained plasma THC, 11-OH-THC and THCCOOH concentration data were obtained over 168 h from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on 2 occasions. Bayesian estimates of the THC pharmacokinetic model from each individual for each dose were fixed prior to the sequential pharmacokinetic analysis of the metabolites.RESULTS:
A 3-compartment model of THC was developed that has a steady-state volume of distribution (VdSS ) of 3401 ± 788 L and a clearance of 0.72 ± 0.10 L/min. 11-OH-THC was characterized by 50 ± 6% of the THC being directly cleared to a 3-compartment model with a VdSS of 415.2 ± 4.3 L and clearance of 0.78 ± 0.05 L/min. The THCCOOH model shared the central compartment of the 11-OH-THC model with a VdSS of 29.1 ± 0.05 L and a clearance of 0.12 ± 0.02 L/min. First order kinetics were observed for THC and THCCOOH between the low and high doses, but a nonlinear pattern was observed for 11-OH-THC.CONCLUSION:
We describe the pharmacokinetics of THC, 11-OH-THC and THCCOOH including inter- and intraindividual variability of the parameter estimates of the model.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cannabis
/
Fumar Maconha
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article