|THC,THC-OH,THC-COOH||metabolism in humans via experiment||Minimal Physiologically Based Pharmacokinetic Model of Intravenously and Orally Administered Delta-9-Tetrahydrocannabinol in Healthy Volunteers.||May 2019|
Ingestion Method: oral 10, 25 and 50 mg THC, 0.1 mg/kg IV|
When administered via the IV or inhalation routes, induction or inhibition of CYP2C9 should be non-contributory as the elimination of THC is dependent only on liver blood flow. THC-OH is also a high extraction ratio drug, but its hepatic clearance is significantly impacted by the hepatic diffusional barrier that impedes its access to hepatic CYP2C9. THC-COOH is glucuronidated and renally cleared; subjects homozygous for CYP2C9*3 have reduced exposure to this metabolite as a result of the polymorphism reducing THC production, the hepatic diffusional barrier impeding egress from the hepatocyte, and increased renal clearance.