MDR1 genotypes do not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic males.
OBJECTIVE
To investigate the influence of three single nucleotide polymorphisms (SNPs) in exon 12 (C1236T), exon 21 (G2677T/A) and exon 26 (C3435T) of MDR1 gene on the absorption of valacyclovir after a single oral administration in the Chinese Han ethnic population.


METHODS
Two hundred healthy Chinese subjects were genotyped for the SNPs of C1236T, G2677T/A and C3435T in the MDR1 gene using allele-specific polymerase chain reaction. Linkage disequilibrium (LD) was analysed. Twenty-four subjects derived from a large random sample (n = 200) received a single oral dose of 600 mg valacyclovir. Plasma concentrations of acyclovir were determined up to 14 h after administration to obtain a pharmacokinetic profile.


RESULTS
LD existed between G2677T/A in exon 21 and C3435T in exon 26 (P < 0.001), between C1236T in exon 12 and C3435T (P < 0.001), but not between C1236T and G2677T/A (P > 0.05). C(max), AUC(0-1.5 h) and AUC(0-infinity) were used as indices of valacyclovir absorption. AUC(0-infinity) for the 2677TA genotype was 17.45 +/- 2.40 microg x h/ml, which was much higher compared with the 2677GG, GA and TT genotypes of 10.44 +/- 1.00, 11.84 +/- 2.83, 11.34 +/- 2.32 microg x h/ml, respectively (P < 0.05). Similarly, a statistically significant difference of AUC(0-infinity) was also observed for different linked genotypes at position 2677 vs. 3435, and 1236 vs. 3435 (P < 0.05). However, there was no significant difference in valacyclovir absorptive pharmacokinetics between carriers and noncarriers of different haplotypes (P > 0.05).


CONCLUSIONS
Three SNPs of MDR1 gene did not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic subjects.
Zhang
Yan
Y
West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
Jiang
Xue-Hua
XH
Hu
Yu-Qin
YQ
Li
Zhi-Ru
ZR
Su
Lan
L
Wang
Zhan-Guo
ZG
Ma
Guo
G
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005091:Exons / Q000235:genetics; D019450:Genes, MDR / Q000187:drug effects / Q000235:genetics*; D008040:Genetic Linkage / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007408:Intestinal Absorption / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000998:Antiviral Agents; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir