ArticleFrontiers in pharmacology2026
Coproporphyrin I PBPK model in the open systems pharmacology suite enables precise prediction of OATP 1B- mediated drug interactions through calibrated
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Organic Anion Transporting Polypeptide (OATP) 1B1/3 inhibition can lead to clinically significant drug-drug interactions (DDIs). Coproporphyrin-I (CP-I) is an established endogenous biomarker for assessing the OATP1B inhibitory activity of new chemical entities. However, current physiologically based pharmacokinetic (PBPK) models for CP-I are restricted to proprietary software, limiting widespread adoption and collaboration. Methods: We developed and qualified an open-source PBPK model for CP-I using the Open Systems Pharmacology (OSP) Suite. The model describes the endogenous synthesis and OATP1B1/MRP2-mediated disposition of CP-I. It was integrated into a DDI network comprising the precipitants rifampicin, probenecid, and cyclosporine A, and the object drugs atorvastatin, pitavastatin, and rosuvastatin. A key methodological feature was the estimation of Results: The CP-I model successfully captured baseline plasma concentration-time profiles with a Geometric Mean Fold Error (GMFE) of 1.15. In the DDI network analysis, using CP-I-derived Conclusion: This study presents a qualified, freely available PBPK framework for CP-I. It demonstrates that calibrating participant models using early clinical biomarker data enables reliable prospective prediction of OATP1B-mediated DDIs. This workflow supports model-informed drug development (MIDD) strategies, potentially reducing the need for dedicated clinical DDI studies.
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