UGT2B7*3 did not affect the pharmacokinetics of R- and S-carvedilol in healthy Japanese.
We previously investigated the pharmacokinetics of R- and S-carvedilol in 54 healthy Japanese subjects, and reported that the oral clearance (CL/F) and apparent volume of distribution (V/F) of both enantiomers in subjects with the CYP2D6*10 allele were significantly lower than those in subjects without the CYP2D6*10 allele. In the present study, we examined the genotype of UGT2B7 in these 54 subjects, and investigated the effect of UGT2B7*3 on the pharmacokinetics of R- and S-carvedilol. Forty-three subjects did not have the UGT2B7*3 allele, and 11 subjects had one UGT2B7*3 allele. CL/F and V/F values of R- and S-carvedilol in the subjects with one UGT2B7*3 allele were similar to those without the UGT2B7*3 allele, indicating that the UGT2B7*3 allele did not significantly affect the systemic clearance (CL) and bioavailability (F) of the two enantiomers.
Honda
Mutsuko
M
Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Toyoda
Wakako
W
Shimizu
Takako
T
Horiuchi
Isao
I
Kayano
Yuichiro
Y
Taguchi
Masato
M
Nozawa
Takashi
T
Inoue
Hiroshi
H
Hashimoto
Yukiya
Y
D000284:Administration, Oral; D018674:Adrenergic Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000077261:Carvedilol; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007564:Japan; D008297:Male; D008657:Metabolic Clearance Rate; D010641:Phenotype; D011110:Polymorphism, Genetic; D011412:Propanolamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D012016:Reference Values; D013237:Stereoisomerism
D018674:Adrenergic Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase