Effects of organic anion transporting polypeptide 1B1 haplotype on pharmacokinetics of pravastatin, valsartan, and temocapril

Abstract

The major clearance mechanism of pravastatin, valsartan, and temocapril appears to be similar, and OATP1B1*1b is one of the determinant factors governing the interindividual variability in the pharmacokinetics of pravastatin and, possibly, valsartan and temocapril.

Pharmacokinetic interaction between pravastatin and olmesartan in relation to SLCO1B1 polymorphism

“…Particularly subjects having SLCO1B1*15 allele (possessing both 388A [G and 521T[C) showed elevated systemic exposure of pravastatin as compared to subjects without this allele (Niemi et al 2004;Nishizato et al 2003). In contrast, some reports indicated that SLCO1B1*1b allele (possessing 388A [G) showed enhanced transport activity of OATP1B1 as compared with wild-type allele (i.e., *1a allele) (Maeda et al 2006;Mwinyi et al 2004).…”

“…In this study, we interpreted data in terms of the sum of pravastatin and RMS-416. This method has been suggested previously in a study by Maeda et al (2006) who demonstrated that RMS-416 is also a substrate of OATP1B1 and assumed that SLCO1B1 variants would affect the pharmacokinetics of the sum of pravastatin and RMS-416 more markedly than that of pravastatin itself. With this assumption, they could observe an increasing trend in AUC of the sum of pravastatin and RMS-416 in subjects with the *15 allele as compared with subjects without the *15 allele (Maeda et al 2006).…”

“…This method has been suggested previously in a study by Maeda et al (2006) who demonstrated that RMS-416 is also a substrate of OATP1B1 and assumed that SLCO1B1 variants would affect the pharmacokinetics of the sum of pravastatin and RMS-416 more markedly than that of pravastatin itself. With this assumption, they could observe an increasing trend in AUC of the sum of pravastatin and RMS-416 in subjects with the *15 allele as compared with subjects without the *15 allele (Maeda et al 2006). Our present findings are in line with their results that the mean AUC 0-24 values in single-dose and co-administration phases of *15/*15 group were 96 and 98% higher than those of the *1b/*1b group, respectively, when compared in terms of the sum of pravastatin and RMS-416.…”

Association study of genetic polymorphisms of drug transporters, SLCO1B1, SLCO1B3 and ABCC2, in African-Americans, Hispanics and Caucasians and olmesartan exposure

“…Both AGAAA and GAAT haplotypes include SNP 505 (underlined), registered in dbSNP as rs2306283 and located in exon 5, which was reported as the functionally important SNP 388A4G (N130D). 37,38 Two human studies on the pharmacokinetic profile of pravastatin reported that 388A4G was associated with increased transport activity of organic anion-transporting polypeptide 1B1, leading to lower AUC of pravastatin in subjects having G allele position at 505. 37,38 Higher AUC values in subjects with A allele may be due to SNP 388A4G; however, these trends were not statistically significant.…”

Further Studies to Support the Use of Coproporphyrin I and III as Novel Clinical Biomarkers for Evaluating the Potential for Organic Anion Transporting Polypeptide 1B1 and OATP1B3 Inhibition

“…Previous studies have shown that SLCO1B1 c388 A > G SNP is strongly linked to elevated activity of OATP1B1, resulting in 10.4 to 31.7% lower AUC of many OATP1B1 substrate drugs (Mwinyi et al, 2004, Lee et al, 2005, Maeda et al, 2006, Yamada et al, 2011, Birmingham et al, 2015a, Choi et al, 2015, Zhao et al, 2017. It is worth noting that these findings have not been confirmed in additional studies examining changes in the transport of other OATP substrates (Lee et al, 2005, Choi et al, 2008, Birmingham et al, 2015b.…”