Article date: August 2008
By: Yan Zhang, Xue‐Hua Jiang, Yu‐Qin Hu, Zhi‐Ru Li, Lan Su, Zhan‐Guo Wang, Guo Ma, in Volume 66, Issue 2, pages 247-254
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
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). Cmax, AUC0–1.5 h and AUC0–∞ were used as indices of valacyclovir absorption. AUC0–∞ 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 AUC0–∞ 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.
DOI: 10.1111/j.1365-2125.2008.03189.x
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