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MDR1 genotypes do not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic males
Author(s) -
Zhang Yan,
Jiang XueHua,
Hu YuQin,
Li ZhiRu,
Su Lan,
Wang ZhanGuo,
Ma Guo
Publication year - 2008
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2008.03189.x
Subject(s) - exon , single nucleotide polymorphism , linkage disequilibrium , genotype , genetics , allele , population , biology , polymorphism (computer science) , gene , medicine , environmental health
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The absorption of valacyclovir presents a highly negative correlation with the level of P‐glycoprotein expression. • It has been confirmed that a polymorphism of the MDR1 gene in exon 26 is related to the level of P‐glycoprotein expression in intestine. • This study was conducted to find the relationship between polymorphism of MDR1 gene and absorption of valacyclovir. WHAT THIS STUDY ADDS • Linkage disequilibrium exists between G2677T/A in exon 21 and C3435T in exon 26, between C1236T in exon 12 and C3435T, but not between C1236T and G2677T/A of MDR1 gene in the Chinese Han ethnic population. • Three single nucleotide polymorphisms of MDR1 gene do not influence the absorption of valacyclovir in the healthy Chinese Han ethnic population. AIMS 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–∞ were used as indices of valacyclovir absorption. AUC 0–∞ for the 2677TA genotype was 17.45 ± 2.40 µg × 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 µg × h/ml, respectively ( P < 0.05). Similarly, a statistically significant difference of AUC 0–∞ 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.