Effect of Steady-State Faldaprevir on Pharmacokinetics of Atorvastatin or Rosuvastatin in Healthy Volunteers: A Prospective Open-Label, Fixed-Sequence Crossover Study

Journal of Clinical Pharmacology
Fenglei HuangSebastian Haertter

Abstract

Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1. Subjects subsequently received 240 mg twice daily of faldaprevir (loading dose) on day 5, followed by 240 mg faldaprevir once daily from day 6 to day 10, with an additional single dose of atorvastatin (10 mg) or rosuvastatin (10 mg) given on day 10. PK samples for the statins were collected on days 1-3 and days 10-12. Concomitant administration with faldaprevir led to approximately 9-fold and 34-fold increases in AUC0-∞ and Cmax , respectively, of atorvastatin and approximately 15-fold and 33-fold increases in AUC0-∞ and Cmax , respectively, of rosuvastatin, compared with the statins given alone. Exposure to the major metabolites (ortho-hydroxyatorvastatin and N-desmethylrosuvastatin) was increased to a ...Continue Reading

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Citations

Mar 21, 2020·Journal of Clinical Pharmacology·Savannah J McFeelyIsabelle Ragueneau-Majlessi
May 29, 2020·Clinical and Translational Science·Roberta Natália CestariVera Lucia Lanchote
Jun 28, 2020·Clinical Pharmacology in Drug Development·Patricia N Sidharta, Jasper Dingemanse
May 3, 2019·British Journal of Clinical Pharmacology·Marco PrevisdominiAlessandro Ceschi
Jul 31, 2020·Expert Opinion on Drug Metabolism & Toxicology·Takeshi HirotaIchiro Ieiri
Feb 11, 2021·Personalized Medicine·Brian TomlinsonChristopher Wk Lam

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