Effect of the hepatitis C virus protease inhibitor telaprevir on the 1 pharmacokinetics of amlodipine and atorvastatin 2 3 4

23 24 Purpose: Telaprevir is a hepatitis C virus protease inhibitor that is both a substrate and 25 an inhibitor of CYP3A. Amlodipine and atorvastatin are both substrates of CYP3A and 26 are amongst the drugs most frequently used by patients with hepatitis C. This study was 27 conducted to examine the effect of telaprevir on atorvastatin and amlodipine 28 pharmacokinetics (PK). 29 Methods: This was an open-label, single sequence, non-randomized study enrolling 21 30 healthy male and female volunteers. A co-formulation of 5 mg amlodipine and 20 mg 31 atorvastatin was administered on Day 1. Telaprevir was dosed as 750 mg q8h with food 32 from Day 11 until Day 26 and a single dose of amlodipine/atorvastatin combination was 33 re-administered on Day 17. Plasma samples were collected for determining the PK of 34 telaprevir, amlodipine, atorvastatin, ortho-hydroxy atorvastatin, and para-hydroxy 35 atorvastatin. 36 Results: When administration with or without telaprevir was compared, the least-squares 37 mean ratios (90% confidence limits) for amlodipine were 1.27 (1.21; 1.33) for Cmax and 38 2.79 (2.58; 3.01) for AUC0-∞; and for atorvastatin were 10.6 (8.74; 12.9) for Cmax and 39 7.88 (6.84; 9.07) for AUC0-∞. 40 Conclusions: Telaprevir significantly increased the exposure to amlodipine and 41 atorvastatin, consistent with the inhibitory effect of telaprevir on the CYP3A-mediated 42 metabolism of these agents. 43 on O cber 2, 2017 by gest httpaac.asm .rg/ D ow nladed fom