Population pharmacokinetic modeling of plasma Δ9-tetrahydrocannabinol and an active and inactive metabolite following controlled smoked cannabis administration.
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. 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. A 3-compartment model of THC was developed that has a steady-state volume of distribution (Vd We describe the pharmacokinetics of THC, 11-OH-THC and THCCOOH including inter- and intraindividual variability of the parameter estimates of the model.