Pub. Date : 2019 Oct
PMID : 31114948
6 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Cytochrome P450 (CYP) 2C9, the primary enzyme responsible for THC metabolism, has two single nucleotide polymorphisms-Arg144Cys (*2) and Ile359Leu (*3). | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 2 | We therefore sought to characterize the pharmacokinetics of THC and its major metabolites 11-hydroxy-delta-9-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in healthy volunteers with known CYP2C9 status by non-compartmental analysis (NCA), compartmental modeling (CM) and minimal physiologically based pharmacokinetic (mPBPK) modeling. | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 3 | THC hepatic clearance is dependent on the CYP2C9 genetic variant in the population. | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 4 | 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. | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 5 | 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. | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 6 | CONCLUSION: It has recently been reported that the terminal metabolite THC-COOH is active, implying the exposure difference in individuals homozygous for CYP2C9*3 may become therapeutically relevant. | Dronabinol | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |