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To explore the steady-state plasma pharmacokinetics of indinavir in twice daily dosing regimens with and without the co-administration of 100mg ritonavir.Observational pharmacokinetic study.HIV-1-infected individuals who use indinavir alone (1200mg twice daily, n=6), or the combination of 100mg ritonavir twice daily plus either 800mg (n=6), or 1200mg indinavir twice daily (n=2).Steady-state pharmacokinetics of indinavir and ritonavir were assessed by drawing 12 blood samples during an 8-h period after ingestion of the medication.Significant differences were observed for indinavir pharmacokinetics between the dosing regimens indinavir 1200mg twice daily alone and indinavir/ ritonavir 800/100mg twice daily with respect to the mean trough concentration (0.21 and 0.99μg/ml, respectively, P =0.002), the mean maximum concentration (13.79 and 8.74μg/ml, respectively, P =0.028), and for the mean plasma elimination half-life (1.6 and 3.2h, respectively, P =0.001). The combination indinavir/ritonavir 1200/100mg twice daily led to very high exposure to indinavir and was not well tolerated. However, the combination indinavir/ritonavir 800/100mg twice daily was well tolerated and resulted in therapeutic concentrations of indinavir with improved trough concentrations and similar maximum concentrations as observed with the licensed dosage of 800mg three times daily.Combination of indinavir and 100mg ritonavir in twice daily dosing regimens significantly affects the pharmacokinetic profile of indinavir. The results of this observational study provide a pharmacologic basis for the combination of indinavir (800mg) and ritonavir (100mg) in twice daily dosing regimens.