Comparative Study of the Dose-Dependence of OATP1B Inhibition by Rifampicin Using Probe Drugs and Endogenous Substrates in Healthy Volunteers

Pharmaceutical Research
Issey TakeharaHiroyuki Kusuhara

Abstract

To evaluate association of the dose-dependent effect of rifampicin, an OATP1B inhibitor, on the plasma concentration-time profiles among OATP1B substrates drugs and endogenous substrates. Eight healthy volunteers received atorvastatin (1 mg), pitavastatin (0.2 mg), rosuvastatin (0.5 mg), and fluvastatin (2 mg) alone or with rifampicin (300 or 600 mg) in a crossover fashion. The plasma concentrations of these OATP1B probe drugs, total and direct bilirubin, glycochenodeoxycholate-3-sulfate (GCDCA-S), and coproporphyrin I, were determined. The most striking effect of 600 mg rifampicin was on atorvastatin (6.0-times increase) and GCDCA-S (10-times increase). The AUC0-24h of atorvastatin was reasonably correlated with that of pitavastatin (r2 = 0.73) and with the AUC0-4h of fluvastatin (r2 = 0.62) and sufficiently with the AUC0-24h of rosuvastatin (r2 = 0.32). The AUC0-24h of GCDCA-S was reasonably correlated with those of direct bilirubin (r2 = 0.74) and coproporphyrin I (r2 = 0.78), and sufficiently with that of total bilirubin (r2 = 0.30). The AUC0-24h of GCDCA-S, direct bilirubin, and coproporphyrin I were reasonably correlated with that of atorvastatin (r2 = 0.48-0.70) [corrected]. These results suggest that direct bilirubin, G...Continue Reading

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Citations

Oct 14, 2018·The Journal of Pharmacology and Experimental Therapeutics·Shelby BarnettAleksandra Galetin
Jul 4, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kit Wun Kathy CheungLichuan Liu
Mar 21, 2020·Journal of Clinical Pharmacology·Savannah J McFeelyIsabelle Ragueneau-Majlessi
Oct 24, 2018·Pharmaceutical Research·Leslie Z BenetJasleen K Sodhi
Sep 4, 2018·CPT: Pharmacometrics & Systems Pharmacology·Takashi YoshikadoYuichi Sugiyama
Oct 11, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Daiki MoriHiroyuki Kusuhara
Jul 30, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yueping ZhangHong Shen
Jul 25, 2020·Clinical Pharmacology and Therapeutics·Daniel A TatosianS Aubrey Stoch
Oct 11, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Rucha SaneZsuzsanna Gáborik
Dec 9, 2020·CPT: Pharmacometrics & Systems Pharmacology·Hiroyuki TakitaAleksandra Galetin
Feb 4, 2021·Journal of Pediatric Gastroenterology and Nutrition·Norman JungeEva-Doreen Pfister
Jan 19, 2021·Journal of Clinical Pharmacology·Sheng FengYuyan Jin
Apr 22, 2021·Clinical Pharmacology and Therapeutics·Yue XiangLeslie Z Benet
Sep 29, 2021·Clinical Pharmacology and Therapeutics·Mikko NeuvonenMikko Niemi
Oct 3, 2021·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jennifer TangYurong Lai

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