AIM: A validated LC-MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand the utility of both as possible endogenous biomarkers for organic anion-transporting polypeptides (OATP)-mediated drug-drug interactions (DDIs). MATERIALS AND METHODS: Human plasma extracts were analyzed for CP-I and CP-III using a Sciex API 6500+ mass spectrometer. Results: The assay was utilized for plasma samples from a clinical DDI study involving a new chemical entity that presented as an OATP inhibitor in vitro. A formal DDI study, with a probe drug (atorvastatin), was also included as part of the clinical study. CONCLUSION: Changes in CP-I area under the plasma concentration versus time curve (AUC0-48 h) were observed, which were similar to the AUC ratio obtained with atorvastatin. These results support the idea that plasma CP-I may have utility in Phase I by supporting the rapid assessment of OATP inhibition risk.
AIM: A validated LC-MS/MS assay for the quantitation of coproporphyrin-I and -III (CP-I, CP-III) in human plasma has been developed to understand the utility of both as possible endogenous biomarkers for organic anion-transporting polypeptides (OATP)-mediated drug-drug interactions (DDIs). MATERIALS AND METHODS:Human plasma extracts were analyzed for CP-I and CP-III using a Sciex API 6500+ mass spectrometer. Results: The assay was utilized for plasma samples from a clinical DDI study involving a new chemical entity that presented as an OATP inhibitor in vitro. A formal DDI study, with a probe drug (atorvastatin), was also included as part of the clinical study. CONCLUSION: Changes in CP-I area under the plasma concentration versus time curve (AUC0-48 h) were observed, which were similar to the AUC ratio obtained with atorvastatin. These results support the idea that plasma CP-I may have utility in Phase I by supporting the rapid assessment of OATP inhibition risk.
Authors: Nicholas S Jones; Kenta Yoshida; Laurent Salphati; Jane R Kenny; Matthew R Durk; Leslie W Chinn Journal: Clin Pharmacol Ther Date: 2019-09-16 Impact factor: 6.875