Population pharmacokinetics model of THC used by pulmonary route in occasional cannabis smokers

Cannabis is the most widely used illegal drug in the world. Delta-9-tetrahydrocannabinol (THC) is the main source of the pharmacological effect. Some studies have been carried out and showed significant variability in the described models as the values of the estimated pharmacokinetic parameters. The objective of this study was to develop a population pharmacokinetic model for THC in occasional cannabis smokers.Twelve male volunteers (age: 20-28 years, body weight: 62.5-91.0 kg), tobacco (3-8 cigarette per day) and cannabis occasional smokers were recruited from the local community. After ad libitum smoking cannabis cigarette according a standardized procedure, 16 blood samples up to 72 h were collected. Population pharmacokinetic analysis was performed using a non-linear mixed effects model, with NONMEM software. Demographic and biological data were investigated as covariates.A three-compartment model with first-order elimination fitted the data. The model was parameterized in terms of micro constants and central volume of distribution (V1). Normal ALT concentration (6.0 to 45.0 IU/l) demonstrated a statistically significant correlation with k10. The mean values (%Relative Standard Error (RSE)) for k10, k12, k21, k23, k32 and V1 were 0.408 h− 1 (48.8%), 4.070 h− 1 (21.4%), 0.022 h− 1 (27.0%), 1.070 h− 1 (14.3%), 1.060 h− 1 (16.7%) and 19.10 L (39.7%), respectively.We have developed a population pharmacokinetic model able to describe the quantitative relationship between administration of inhaled doses of THC and the observed plasma concentrations after smoking cannabis. In addition, a linear relationship between ALT concentration and value of k10 has been described and request further investigation.