Fevipiprant has a low risk of influencing co-medication pharmacokinetics: Impact on simvastatin and rosuvastatin in different SLCO1B1 genotypes

Publication date: Available online 10 June 2019Source: Pulmonary Pharmacology &TherapeuticsAuthor(s): Birk Poller, Ralph Woessner, Avantika Barve, Hanns-Christian Tillmann, Janardhana Vemula, Alexandra Nica, Walid Elbast, Hilmar Schiller, Peter End, Gian Camenisch, Markus WeissAbstractFevipiprant, a prostaglandin D2 receptor 2 antagonist, is in clinical development as a treatment for asthma. The goal of this study was to assess the potential of fevipiprant to cause drug-drug interactions (DDI) as a perpetrator, that is, by altering the pharmacokinetics (PK) of co-medications.In vitro drug interaction studies of clinically relevant drug metabolizing enzymes and transporters were conducted for fevipiprant and its acyl glucuronide (AG) metabolite. Comparison of Ki values with unbound systemic or portal vein steady-state plasma exposure of fevipiprant and its AG metabolite revealed the potential for inhibition of organic anion transporting polypeptide 1B1 (OATP1B1) transporters (R-value of 5.99), while other targets including cytochrome P450 enzymes were not, or only marginally, inhibited.Consequently, an open-label, two-part, two-period, single-sequence clinical study assessed the effect of fevipiprant 450 mg QD on the pharmacokinetics of simvastatin 20 mg and rosuvastatin 20 mg, two statins with different dependency in OATP1B1-mediated hepatic uptake, in healthy adult volunteers. The study also assessed the pharmacogenetics of the SLCO1B1 gene, which encodes OATP1B1. ...
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research

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