Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9.
The impact of the CYP2C9 polymorphism on the pharmacokinetics of orally administered 9-tetrahydrocannabinol (THC) was studied in 43 healthy volunteers. THC pharmacokinetics did not differ by CYP2C9*2 allele status. However, the median area under the curve of THC was threefold higher and that of 11-nor-9-carboxy-9-tetrahydrocannabinol was 70% lower in CYP2C9*3/*3 homozygotes than in CYP2C9*1/*1 homozygotes. CYP2C9*3 carriers also showed a trend toward increased sedation following administration of THC. Therefore, the CYP2C9*3 variant may influence both the therapeutic and adverse effects of THC.
Sachse-Seeboth
C
C
Department of Clinical Pharmacology, University Medicine, Göttingen, Germany.
Pfeil
J
J
Sehrt
D
D
Meineke
I
I
Tzvetkov
M
M
Bruns
E
E
Poser
W
W
Vormfelde
S V
SV
Brockmöller
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D013759:Dronabinol / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012737:Sex Factors; D055815:Young Adult
D013759:Dronabinol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases