Influence of ABCB1 gene polymorphisms on the pharmacokinetics of verapamil among healthy Chinese Han ethnic subjects.
OBJECTIVE
To assess the association between polymorphisms of the ABCB1 gene and the pharmacokinetics of verapamil among healthy Chinese Han ethnic subjects.


METHODS
Based on polymorphisms of the ABCB1 gene at positions 2677 and 3435, 24 healthy male participants were divided into three groups: 2677GG/3435CC (n = 6), 2677GT/3435CT (n = 12) and 2677TT/3435TT (n = 6). Each subject had received a single oral dose of verapamil (80 mg) under fasting conditions. Multiple blood samples were collected over 24 h, and plasma concentrations of verapamil were determined by HPLC. Pharmacokinetic characteristics were compared between the different genotypic groups.


RESULTS
The pharmacokinetics parameters of verapamil differed significantly among the three genotypic groups. AUC(last) was significantly lower among individuals with the 2677TT/3435TT (159.5 +/- 79.0 ng ml(-1) h) and 2677GT/3435CT (189.3 +/- 73.1 ng ml(-1) h) genotypes than those with the 2677GG/3435CC genotype (303.1 +/- 83.7 ng ml(-1) h) (P= 0.004 and P= 0.008, respectively). However, the CL/F value was higher among subjects with the 2677TT/3435TT (523.0 +/- 173.7 l h(-1)) genotype than those with the 2677GT/3435CT (452.2 +/- 188.6 l h(-1)) or 2677GG/3435CC (265.4 +/- 72.8 l h(-1)) genotypes. A significant difference was also found between the latter two groups (P= 0.034). In addition, the C(max) tended to be higher among subjects with the 2677GG/3435CC genotype than those with the 2677GT/3435CT or 2677TT/3435TT genotypes (42.2 +/- 3.9 vs 32.2 +/- 16.2 vs 38.1 +/- 13.7 ng ml(-1)).


CONCLUSIONS
Our study showed for the first time that verapamil pharmacokinetics may be influenced by particular genetic polymorphisms of the ABCB1 gene among healthy Chinese Han ethnic subjects. An individualized dosage regimen design incorporating such information may improve the efficacy of the drug whilst reducing adverse reactions.
Zhao
Li-Mei
LM
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China. zhaolm@sj-hospital.org
He
Xiao-Jing
XJ
Qiu
Feng
F
Sun
Ya-Xin
YX
Li-Ling
Jesse
J
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D002121:Calcium Channel Blockers / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005838:Genotype; D006207:Half-Life; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014700:Verapamil / Q000493:pharmacokinetics*; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D014700:Verapamil