Emmanuel A, Gillotin C, Farinotti R, Sadler BM; International Conference on AIDS.
Int Conf AIDS. 1998; 12: 90 (abstract no. 12384).
Glaxo Wellcome, Issy-les-Moulineaux, France.
The potential pharmacokinetic interaction between atovaquone and indinavir was investigated in 24 healthy adult volunteers (12 males, 12 females). This was an open-label, randomized, multiple-dose, 3-way cross-over study in which subjects received 750 mg atovaquone bid, 800 mg indinavir tid and 750 mg atovaquone bid + 800 mg indinavir tid. Each treatment was given for 14 days with a 3 week washout period between treatments. Atovaquone was given with food and indinavir while fasted. Blood was sampled at regular intervals during the 2 weeks of dosing and for 336 hours after the last dose of atovaquone or for 24 hours after the last dose of indinavir in each period. Atovaquone and indinavir were assayed using validated HPLC methods. All adverse events were recorded throughout the study. Pharmacokinetic analyses were performed using model-independent methods. Preliminary results indicate that the Cmax and AUCss of atovaquone were increased 16% and 13%, respectively, by coadministration with indinavir. Between indinavir alone and in combination with atovaquone there was a 7% increase in Cmax and a 5% decrease in AUCss. The inter-subject variability was approximately 20% for each treatment. Atovaquone and indinavir were well tolerated alone and in combination. Atovaquone appears to have little effect on the steady-state pharmacokinetics of indinavir. Given the favorable safety profile of atovaquone, the increases observed in Cmax and AUCss are unlikely to be of clinical significance. CONCLUSION: It appears that no dosage adjustments are necessary for either drug when atovaquone and indinavir are given together.
Publication Types:
Keywords:
- Adult
- Atovaquone
- Chromatography, High Pressure Liquid
- Drug Interactions
- Female
- Humans
- Indinavir
- Male
- Naphthoquinones
- blood
- pharmacokinetics
Other ID:
UI: 102227412
From Meeting Abstracts