title: MDR1 genotypes do not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic males.
abstract: 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.
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xue-Hua
authors.initials: XH
authors.lastname: Jiang
authors.forename: Yu-Qin
authors.initials: YQ
authors.lastname: Hu
authors.forename: Zhi-Ru
authors.initials: ZR
authors.lastname: Li
authors.forename: Lan
authors.initials: L
authors.lastname: Su
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Wang
authors.forename: Guo
authors.initials: G
authors.lastname: Ma
mesh_terms: 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
chemical_list: 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