The steady-state plasma pharmacokinetics of indinavir alone and in combination with a low dose of ritonavir in twice daily dosing regimens in HIV-1-infected individuals

Objective: To explore the steady-state plasma pharmacokinetics of indinavir in twice daily dosing regimens with and without the co-administration of 1 00 mg ritonavir. Design: Observational pharmacokinetic study. Patients: HIV-l-infected individuals who use indinavir alone (1200 mg twice daily, n = 6), or the combination of 100 mg ritonavir twice daily plus eit her 800 mg (n = 6), or 1200 mg indinavir twice daily (n = 2). Methods: Steady-state pharmacokinetics of indinavir and ritonavir were asse ssed by drawing 12 blood samples during an 8-h period after ingestion of th e medication. Results: Significant differences were observed for indinavir pharmacokineti cs between the dosing regimens indinavir 1200 mg twice daily alone and indi navir/ritonavir 800/100 mg twice daily with respect to the mean trough conc entration (0.21 and 0.99 mu g/ml, respectively, P = 0.002), the mean maximu m concentration (13.79 and 8.74 mu g/ml, respectively, P = 0.028), and for the mean plasma elimination half-life (1.6 and 3.2 h, respectively, P = 0.0 01). The combination indinavir/ritonavir 1200/100 mg twice daily led to ver y high exposure to indinavir and was not well tolerated. However, the combi nation indinavir/ritonavir 800/100 mg twice daily was well tolerated and re sulted in therapeutic concentrations of indinavir with improved trough conc entrations and similar maximum concentrations as observed with the licensed dosage of 800 mg three times daily. Conclusion: Combination of indinavir and 100 mg ritonavir in twice dairy do sing regimens significantly affects the pharmacokinetic profile of indinavi r. The results of this observational study provide a pharmacologic basis fo r the combination of indinavir (800 mg) and ritonavir (100 mg) in twice dai ly dosing regimens. (C) 1999 Lippincott Williams & Wilkins.