Pharm Res (2018) 35: 138 https://doi.org/10.1007/s11095-018-2416-3 RESEARCH PAPER Comparative Study of the Dose-Dependence of OATP1B Inhibition by Rifampicin Using Probe Drugs and Endogenous Substrates in Healthy Volunteers 1,2 3,4 4 2 5 6 6 Issey Takehara & Takashi Yoshikado & Keiko Ishigame & Daiki Mori & Ken-ichi Furihata & Nobuaki Watanabe & Osamu Ando & 2 4 2 Kazuya Maeda & Yuichi Sugiyama & Hiroyuki Kusuhara Received: 13 January 2018 /Accepted: 22 April 2018 /Published online: 10 May 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018 ABSTRACT reasonably correlated with that of pitavastatin (r = Purpose To evaluate association of the dose-dependent effect 0.73) and with the AUC of fluvastatin (r = 0.62) 0–4h of rifampicin, an OATP1B inhibitor, on the plasma concen- andsufficientlywiththe AUC of rosuvastatin 0–24h tration–time profiles among OATP1B substrates drugs and (r = 0.32). The AUC of GCDCA-S was reasonably 0–24h endogenous substrates. correlated with those of direct bilirubin (r =0.74) and Methods Eight healthy volunteers received atorvastatin coproporphyrin I (r = 0.80), and sufficiently with that of (1 mg), pitavastatin (0.2 mg), rosuvastatin (0.5 mg), and total bilirubin (r = 0.30). The AUC of GCDCA-S, 0–24h fluvastatin (2 mg) alone or
Pharmaceutical Research – Springer Journals
Published: May 10, 2018
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