The effect of CYP3A inhibitors and inducers on the pharmacokinetics of telaprevir in healthy volunteers

Br J Clin Pharmacol. 2013 Feb;75(2):431-9. doi: 10.1111/j.1365-2125.2012.04345.x.


Aim: To evaluate the effects of ketoconazole, rifampicin and efavirenz on the pharmacokinetics of telaprevir in healthy volunteers.

Method: Results from three clinical studies are described. (1) Volunteers received a single 750 mg dose telaprevir with and without a single 400 mg dose ketoconazole. (2) Volunteers received (a) 1250 mg telaprevir followed by three 750 mg doses given every 8 h and (b) four 1250 mg telaprevir doses given every 8 h, with a single 400 mg dose ketoconazole given with the fourth dose of telaprevir. (3) Volunteers received either a single 750 mg dose telaprevir with or without 600 mg once daily rifampicin, or 750 mg every 8 h telaprevir with and without 600 mg once daily efavirenz.

Results: A single 400 mg dose of ketoconazole increased single dose telaprevir exposure: the geometric least-squares mean ratio (GLSMR, with 90% confidence limits) was 1.24 (1.10, 1.41) for C(max) and 1.62 (1.45, 1.81) for AUC(0,∞). However, after multiple doses of telaprevir, there was no discernible effect of ketoconazole on telaprevir exposure. Co-administration of rifampicin at steady-state markedly reduced single dose telaprevir exposure with GLSMRs of 0.14 (0.11, 0.18) for C(max) and 0.08 (0.07, 0.11) for AUC(0,∞), whereas efavirenz had a smaller effect on telaprevir exposure when both drugs were co-administered at steady-state, with GLSMRs of 0.91 (0.81, 1.02) for C(max) , 0.53 (0.44, 0.65) for C(min), and 0.74 (0.65, 0.84) for AUC(0,8 h).

Conclusion: CYP3A inducers, rifampicin and efavirenz, can reduce telaprevir exposure to varying degrees based on their potency. The effect of ketoconazole as an inhibitor of telaprevir metabolism is more pronounced after a single dose of telaprevir than after repeated administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alkynes
  • Area Under Curve
  • Benzoxazines / pharmacology*
  • Clinical Trials as Topic
  • Cyclopropanes
  • Cytochrome P-450 CYP3A / metabolism*
  • Cytochrome P-450 CYP3A Inhibitors*
  • Drug Combinations
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Ketoconazole / pharmacology*
  • Male
  • Middle Aged
  • Oligopeptides / pharmacokinetics*
  • Rifampin / pharmacology*


  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Combinations
  • Enzyme Inhibitors
  • Oligopeptides
  • telaprevir
  • Cytochrome P-450 CYP3A
  • efavirenz
  • Ketoconazole
  • Rifampin