Pharmacogenetics and Genomics
Clinical Pharmacology & Therapeutics (2005) 78, 342–350; doi: 10.1016/j.clpt.2005.07.003
Effect of OATP1B1 (SLCO1B1) variant alleles on the pharmacokinetics of pitavastatin in healthy volunteers*
Jae-Yong Chung MD1, Joo-Youn Cho PhD1, Kyung-Sang Yu MD, PhD1, Jung-Ryul Kim MD1, Dal-Seok Oh OMD1, Hye-Ryung Jung MS1, Kyoung-Soo Lim MD1, Ki-Ho Moon1, Sang-Goo Shin MD, PhD1 and In-Jin Jang MD, PhD1
1Department of Pharmacology and Clinical Pharmacology Unit, Seoul National University College of Medicine and Hospital, and Choongwae Pharma
Correspondence: In-Jin Jang, MD, PhD, Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul, 110-799, Korea E-mail: ijjang@snu.ac.kr
*This study was sponsored by grants from the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (03-PJ10-PG13-GD01-0002), and Choongwae Pharma.
Received 31 January 2005; Accepted 8 July 2005.
Abstract
Background: Pitavastatin is a potent, newly developed 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitor for the treatment of hyperlipidemia. We characterized the effects of organic anion transporting polypeptide 1B1 (OATP1B1) alleles *1a, *1b, and *15 on the pharmacokinetics of pitavastatin.
Methods: Twenty-four healthy Korean volunteers who had previously participated in a pharmacokinetic study of pitavastatin (single oral dose, 1-8 mg) were further investigated. Subjects were grouped according to OATP1B1 genotype. Dose-normalized area under the plasma concentration–time curve (AUC) and peak plasma concentration (Cmax) values were analyzed, because different dosages were administered to subjects, whereas the pharmacokinetics showed linear characteristics.
Results: Dose-normalized pitavastatin AUCs for *1b/*1b (group 1), *1a/*1a or *1a/*1b (group 2), and *1a/*15 or *1b/*15 (group 3) were 38.8 
13.3, 54.4 12.4, and 68.1 16.3 ng 
h mL-1 mg-1 (mean SD), respectively, with significant differences between all 3 groups (P = .008) and between subjects carrying and those not carrying the *15 allele (P = .004). Dose-normalized pitavastatin Cmax values were 13.2 3.3, 18.2 5.7, and 29.4 9.6 ng mL-1 mg-1 in groups 1, 2, and 3, respectively, and also showed significant differences (P = .003) in a manner similar to that shown by AUC. No significant differences were found between the genotype groups in terms of dose-normalized AUC or Cmax values of pitavastatin lactone.
Conclusion: OATP1B1 variant haplotypes were found to have a significant effect on the pharmacokinetics of pitavastatin. These results suggest that the *15 allele is associated with decreased pitavastatin uptake from blood into hepatocytes and that OATP1B1 genetic polymorphisms have no effect on the pharmacokinetics of pitavastatin lactone.
