Impact of ABCC2, ABCG2 and SLCO1B1 Polymorphisms on the Pharmacokinetics of Pitavastatin in Humans

Summary: Pitavastatin, a 3-hydroxyl-3-methylglutaryl-coenzyme A reductase inhibitor is distributed to the liver, a target organ of action and excreted mainly into the bile. To investigate the impact of influx (OATP1B1) and efflux (MRP2, BCRP) transporter alleles on its disposition, the pharmacokinetic (PK) parameters were compared among the following groups: SLC01B1 (*15 carrier and non-carrier), ABCC2 (G1249A, C3972T, C–24 T, G1549A, and G1774T), and ABCG2 (C421A) single nucleotide polymorphisms in 45 healthy Korean volunteers. Pitavastatin AUClast was higher in individuals carrying the SLC01B1*15 allele than those not carrying it (144.1 ± 55.3 vs 84.7 ± 25.7 h-ng/mL [mean ± SD], p = 0.002). The AUC last varied significantly according to the ABCC2 C–24 T allele (103.4 ± 42.2, 80.2 ± 23.8, and 39.0 h-ng/mL in CC, CT and TT, respectively; p = 0.027). Other SNPs of ABCC2 and ABCG2 were not significant. The effect of these transporters and body weight on the AUC last and C max were tested, and only SLC01B1 and ABCC2 C–24 T genotypes were significant factors by analysis of covariance. These variants accounted for almost 50% of the variation in AUC last and C max of pitavastatin. Therefore, ABCC2 C–24 T was significantly associated with pitavastatin human PK when the known effect of SLC01B1 *15 was also considered.