Influence of ALDH2 genetic polymorphisms on aciclovir pharmacokinetics following oral administration of valaciclovir in Japanese end-stage renal disease patients.
This study was performed to investigate the pharmacokinetics of valaciclovir (VACV), aciclovir (ACV) and 9-(carboxymethoxy)methylguanine (CMMG) in Japanese chronic hemodialysis patients following a single oral administration of 1000 mg VACV and the influence of genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) on their pharmacokinetics. A total of eighteen individuals genotyped as ALDH2*1/*1, ALDH2*1/*2 or ALDH2*2/*2 were enrolled in this study. Blood samples were obtained pre-dose and up to 48 hour post-dose. ACV t(1/2) was significantly affected by ALDH2 genotype and prolonged in the order of ALDH2*1/*1 (18.1 hr)<ALDH2*1/*2 (21.9 hr)<ALDH2*2/*2 (26.7 hr). ACV AUC from zero to infinity (AUC(0-infinity)) increased with prolonged ACV t(1/2). ACV C(max) was similar across the three ALDH2 genotype groups. There was no apparent relationship between ALDH2 genotype and VACV or CMMG pharmacokinetics. This is the first study to show an association between ALDH2 genetic polymorphisms and ACV elimination rate (t(1/2)) in Japanese end-stage renal disease patients.
Hara
Katsutoshi
K
Clinical Pharmacology Department, GlaxoSmithKline K.K., Tokyo, Japan. Katsutoshi.2.Hara@gsk.com
Suyama
Kazuaki
K
Itoh
Hiroshi
H
Nagashima
Satoru
S
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011355:Prodrugs / Q000008:administration & dosage*; D006435:Renal Dialysis; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D011355:Prodrugs; D006147:Guanine; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D014633:Valine; D000077483:Valacyclovir; C035400:9-carboxymethoxymethylguanine; D000212:Acyclovir