Effect of OATP1B1 genotypes on plasma concentrations of endogenous OATP1B1 substrates and drugs, and their association in healthy volunteers

• Published in: Drug metabolism and pharmacokinetics Vol. 34; no. 1; pp. 78 - 86
• Main Authors: Mori, Daiki, Kashihara, Yushi, Yoshikado, Takashi, Kimura, Miyuki, Hirota, Takeshi, Matsuki, Shunji, Maeda, Kazuya, Irie, Shin, Ieiri, Ichiro, Sugiyama, Yuichi, Kusuhara, Hiroyuki
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2019
• Subjects: Adult; Biomarker; Coproporphyrin I; Endogenous substrate; Female; Gender difference; Genotype; Healthy Volunteers; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - blood; Liver-Specific Organic Anion Transporter 1 - blood; Liver-Specific Organic Anion Transporter 1 - genetics; Male; OATP1B1 genotype; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - blood; Statin; Substrate Specificity - physiology; Young Adult; GCDCA-S; Endogenous substrate; Biomarker; CDCA-24G; Coproporphyrin I; Gender difference; DDI; OATP1B3; MRM; Statin; LC–MS/MS; OATP1B1; AUC; CV; CP-I; OCT2; MATE1; TLCA-S; OATP1B1 genotype; LCA-S; GLCA-S

This study aimed to elucidate the impact of OATP1B1 genotype (*1b/*1b, *1b/*15, and *15/*15) on plasma concentrations of endogenous OATP1B1 substrates. Healthy volunteers with OATP1B1 *1b/*1b (n = 10), *1b/*15 (n = 7), or *15/*15 (n = 2) received oral administration of a cocktail of statins (atorvas...