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

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Hong ShenW Griffith Humphreys

Abstract

In a recent study, limited to South Asian Indian subjects (n = 12), coproporphyrin (CP) I and CPIII demonstrated properties appropriate for an organic anion-transporting polypeptide (OATP) 1B endogenous probe. The current studies were conducted in healthy volunteers of mixed ethnicities, including black, white, and Hispanic subjects, to better understand the utility of these biomarkers in broader populations. After oral administration with 600 mg rifampin, AUC(0-24h) values were 2.8-, 3.7-, and 3.6-fold higher than predose levels for CPI and 2.6-, 3.1-, and 2.4-fold higher for CPIII, for the three populations, respectively. These changes in response to rifampin were consistent with previous results. The sensitivity toward OATP1B inhibition was also investigated by evaluating changes of plasma CP levels in the presence of diltiazem and itraconazole [administered as part of an unrelated drug-drug interaction (DDI) investigation], two compounds that were predicted to have minimal inhibitory effect on OATP1B. Administration of diltiazem and itraconazole did not increase plasma CPI and CPIII concentrations relative to prestudy levels, in agreement with predictions from in vitro parameters. Additionally, the basal CP concentrations i...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
Dec 28, 2019·Drug Metabolism and Disposition : the Biological Fate of Chemicals·A David RodriguesStefan Oswald
Jul 30, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yueping ZhangHong Shen
Dec 9, 2020·CPT: Pharmacometrics & Systems Pharmacology·Hiroyuki TakitaAleksandra Galetin
Jan 19, 2021·Journal of Clinical Pharmacology·Sheng FengYuyan Jin
Sep 29, 2021·Clinical Pharmacology and Therapeutics·Mikko NeuvonenMikko Niemi

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