Unknown

Dataset Information

0

Dose-Dependent Inhibition of OATP1B by Rifampicin in Healthy Volunteers: Comprehensive Evaluation of Candidate Biomarkers and OATP1B Probe Drugs.


ABSTRACT: To address the most appropriate endogenous biomarker for drug-drug interaction risk assessment, eight healthy subjects received an organic anion transporting polypeptide 1B (OATP1B) inhibitor (rifampicin, 150, 300, and 600 mg), and a probe drug cocktail (atorvastatin, pitavastatin, rosuvastatin, and valsartan). In addition to coproporphyrin I, a widely studied OATP1B biomarker, we identified at least 4 out of 28 compounds (direct bilirubin, glycochenodeoxycholate-3-glucuronide, glycochenodeoxycholate-3-sulfate, and hexadecanedioate) that presented good sensitivity and dynamic range in terms of the rifampicin dose-dependent change in area under the plasma concentration-time curve ratio (AUCR). Their suitability as OATP1B biomarkers was also supported by the good correlation of AUC0-24h between the endogenous compounds and the probe drugs, and by nonlinear regression analysis (AUCR-1 vs. rifampicin plasma Cmax (maximum total concentration in plasma)) to yield an estimate of the inhibition constant of rifampicin. These endogenous substrates can complement existing OATP1B-mediated drug-drug interaction risk assessment approaches based on agency guidelines in early clinical trials.

SUBMITTER: Mori D 

PROVIDER: S-EPMC7158214 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Dose-Dependent Inhibition of OATP1B by Rifampicin in Healthy Volunteers: Comprehensive Evaluation of Candidate Biomarkers and OATP1B Probe Drugs.

Mori Daiki D   Kimoto Emi E   Rago Brian B   Kondo Yusuke Y   King-Ahmad Amanda A   Ramanathan Ragu R   Wood Linda S LS   Johnson Jillian G JG   Le Vu H VH   Vourvahis Manoli M   David Rodrigues A A   Muto Chieko C   Furihata Kenichi K   Sugiyama Yuichi Y   Kusuhara Hiroyuki H  

Clinical pharmacology and therapeutics 20200101 4


To address the most appropriate endogenous biomarker for drug-drug interaction risk assessment, eight healthy subjects received an organic anion transporting polypeptide 1B (OATP1B) inhibitor (rifampicin, 150, 300, and 600 mg), and a probe drug cocktail (atorvastatin, pitavastatin, rosuvastatin, and valsartan). In addition to coproporphyrin I, a widely studied OATP1B biomarker, we identified at least 4 out of 28 compounds (direct bilirubin, glycochenodeoxycholate-3-glucuronide, glycochenodeoxych  ...[more]

Similar Datasets

| S-EPMC1764434 | biostudies-literature
| S-EPMC11303472 | biostudies-literature
| S-EPMC9199885 | biostudies-literature
| S-EPMC5794840 | biostudies-literature
| S-EPMC7847648 | biostudies-literature
| S-EPMC6105874 | biostudies-other
| S-EPMC10117888 | biostudies-literature
| S-EPMC8653087 | biostudies-literature
| S-EPMC4872435 | biostudies-literature
| S-EPMC4505278 | biostudies-literature