Population pharmacokinetic modeling of plasma Δ9‐tetrahydrocannabinol and an active and inactive metabolite following controlled smoked cannabis administration
Year: 2019
Type: article
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.
DOI: 10.1111/bcp.14170
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2989601590