Effect of efavirenz treatment on the pharmacokinetics of nelfinavir boosted by ritonavir in healthy volunteers

Br J Clin Pharmacol. 2004 Dec;58(6):632-40. doi: 10.1111/j.1365-2125.2004.02214.x.


Aims: A once-daily (q.d.) nucleoside-sparing regimen can prevent mitochondrial toxicity, overcome viral resistance and improve compliance. In the present study the effect of efavirenz on the pharmacokinetics and tolerability of once-daily nelfinavir/ritonavir was evaluated in healthy subjects.

Methods: This was a multiple-dose, open-label, single-group, two-period study in 24 healthy subjects. Each received from days 1-10 (period 1): 1875 mg nelfinavir plus 200 mg ritonavir q.d. with a 300-kcal snack. During days 11-20 (period 2) efavirenz 600 mg q.d. was added to the regimen. Blood samples were collected up to 24 h after dosing on days 10 (period 1) and 20 (period 2). High-performance liquid chromatography methods were used for the determination of the concentrations of all compounds. The main pharmacokinetic parameters were calculated using noncompartmental methods.

Results: All subjects completed the study. After the first period mean nelfinavir AUC(0-24 h), C(max) and C(24) were 49.6 mg h(-1) l(-1), 5.0 mg l(-1) and 0.37 mg l(-1), and the sum of nelfinavir plus its active metabolite M8 C(24) was 0.83 mg l(-1). The relative bioavailability, expressed as a geometric mean ratio (90% confidence interval) for nelfinavir AUC(0-24 h), C(max) and C(24) of period 2 compared with period 1 was: 1.30 (1.21, 1.40), 1.29 (1.19, 1.40) and 1.48 (1.32, 1.66). The sum of nelfinavir and M8 C(24) in period 2 was 0.99 mg l(-1), an increase of 19%. No serious adverse events occurred.

Conclusions: The studied regimens were well tolerated. Nelfinavir/ritonavir given together with efavirenz resulted in a 48% higher mean C(24) concentration for nelfinavir, and the sum of nelfinavir and M8 C(24) concentrations was 0.99 mg l(-1). Efavirenz exposure in this study was similar to that reported previously, and therefore can be used effectively in combination with ritonavir and nelfinavir.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • Female
  • HIV Protease Inhibitors / administration & dosage
  • HIV Protease Inhibitors / blood
  • HIV Protease Inhibitors / pharmacokinetics*
  • Humans
  • Male
  • Middle Aged
  • Nelfinavir / administration & dosage
  • Nelfinavir / blood
  • Nelfinavir / pharmacokinetics*
  • Oxazines / blood
  • Oxazines / pharmacology*
  • Reverse Transcriptase Inhibitors / blood
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Ritonavir / administration & dosage
  • Ritonavir / blood
  • Ritonavir / pharmacokinetics*


  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Drug Combinations
  • HIV Protease Inhibitors
  • Oxazines
  • Reverse Transcriptase Inhibitors
  • Nelfinavir
  • efavirenz
  • Ritonavir