title: Influence of ABCC2, SLCO1B1, and ABCG2 polymorphisms on the pharmacokinetics of olmesartan.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea.
authors.forename: Choon O
authors.initials: CO
authors.lastname: Kim
authors.forename: Sung K
authors.initials: SK
authors.lastname: Cho
authors.forename: Eun S
authors.initials: ES
authors.lastname: Oh
authors.forename: Min S
authors.initials: MS
authors.lastname: Park
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Chung
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005838:Genotype; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D000068557:Olmesartan Medoxomil; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056910:Republic of Korea; D013777:Tetrazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000959:Antihypertensive Agents; D007093:Imidazoles; D027381:Liver-Specific Organic Anion Transporter 1; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D000068557:Olmesartan Medoxomil; D027361:Organic Anion Transporters; D013777:Tetrazoles; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C503999:SLCO1B1 protein, human