MDR1 genotypes do not influence the absorption of a single oral dose of 600 mg valacyclovir in healthy Chinese Han ethnic males
| Autor: | Guo Ma, Zhan-Guo Wang, Lan Su, Zhi-Ru Li, Xue-Hua Jiang, Yan Zhang, Yu-Qin Hu |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Linkage disequilibrium ATP Binding Cassette Transporter Subfamily B Genotype Genetic Linkage Population Acyclovir Administration Oral Single-nucleotide polymorphism Biology Pharmacology physiological processes Antiviral Agents Polymorphism Single Nucleotide Intestinal absorption Exon Asian People Polymorphism (computer science) Internal medicine medicine polycyclic compounds Humans Pharmacology (medical) ATP Binding Cassette Transporter Subfamily B Member 1 education neoplasms education.field_of_study Dose-Response Relationship Drug Haplotype virus diseases Valine Exons Endocrinology Treatment Outcome Intestinal Absorption Pharmacogenetics Area Under Curve Valacyclovir Genes MDR |
| Zdroj: | British journal of clinical pharmacology. 66(2) |
| ISSN: | 1365-2125 |
| Popis: | 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 0.05). 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). 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. |
| Databáze: | OpenAIRE |
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