Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea.
J Cardiovasc Pharmacol. 2012 Jul;60(1):49-54. doi: 10.1097/FJC.0b013e3182576098.
This study was designed to determine whether genetic polymorphisms of multidrug-resistant protein 2 (ABCC2), organic anion transporting polypeptide 1B1 (SLCO1B1), and breast cancer resistance protein (ABCG2) have an effect on olmesartan pharmacokinetics in Korean subjects. Sixty-eight healthy male volunteers who participated in previous pharmacokinetics studies of olmesartan medoxomil (single dose, 20 mg or 40 mg) were enrolled. All subjects were analyzed and grouped according to the genotypes of ABCC2, SLCO1B1, and ABCG2. The dose-normalized peak plasma concentration (C(max)) and area under the plasma concentration-time curve (AUCt) values were analyzed. The dose-normalized mean C(max) and AUC(t) in the ABCC2 -24CT genotype group were higher than those in the -24CC genotype group [C(max,dn): CT 26.1 ± 6.5 (ng/mL)/mg versus CC 22.1 ± 6.7 (ng/mL)/mg, P = 0.010, AUC(t,dn): CT 178.7 ± 45.6 (hr·ng(-1)·mL(-1))/mg versus CC 149.9 ± 39.8 (hr·ng(-1)·mL(-1))/mg, P = 0.010]. The difference in AUC(t,dn) between the ABCC2 -1549GG and -1549GA genotype groups was statistically significant [GG 149.0 ± 41.0 (hr·ng(-1)·mL(-1))/mg versus GA 174.1 ± 43.3 (hr·ng(-1)·mL(-1))/mg, P = 0.019]. No significant differences were observed for any other single nucleotide polymorphism in ABCC2, SLCO1B1, or ABCG2. The ABCC2 -24CC genotype group exhibited lower systemic exposure of olmesartan than the -24CT genotype group, whereas no significant differences were observed in the other transporter genotype groups.
本研究旨在探讨多药耐药相关蛋白 2（ABCC2）、有机阴离子转运多肽 1B1（SLCO1B1）和乳腺癌耐药蛋白（ABCG2）的基因多态性是否会影响韩国人群中奥美沙坦的药代动力学。共纳入 68 名曾参与奥美沙坦镁单剂量（20mg 或 40mg）药代动力学研究的健康男性志愿者。根据 ABCC2、SLCO1B1 和 ABCG2 的基因型对所有受试者进行分析和分组。分析了药物标准化后的峰血浆浓度（C(max)）和血浆浓度-时间曲线下面积（AUCt）。ABCC2-24CT 基因型组的药物标准化平均 C(max)和 AUC(t) 高于 -24CC 基因型组[C(max,dn): CT 26.1 ± 6.5（ng/mL）/mg 比 CC 22.1 ± 6.7（ng/mL）/mg，P=0.010，AUC(t,dn): CT 178.7 ± 45.6（hr·ng(-1)·mL(-1))/mg 比 CC 149.9 ± 39.8（hr·ng(-1)·mL(-1))/mg，P=0.010]。ABCC2-1549GG 和 -1549GA 基因型组间 AUC(t,dn) 的差异具有统计学意义[GG 149.0 ± 41.0（hr·ng(-1)·mL(-1))/mg 比 GA 174.1 ± 43.3（hr·ng(-1)·mL(-1))/mg，P=0.019]。ABCC2、SLCO1B1 或 ABCG2 中任何其他单核苷酸多态性均无显著差异。ABCC2-24CC 基因型组的奥美沙坦系统暴露量低于 -24CT 基因型组，而其他转运体基因型组间无显著差异。
