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• W2146027341 abstract "ABSTRACT Therapeutic control of human immunodeficiency virus type 1 (HIV-1) in peripheral compartments does not assure control in the central nervous system. Inadequate drug penetration may provide a sanctuary from which resistant virus can emerge or allow development of psychomotor abnormalities. To characterize the effect of ritonavir on indinavir disposition into cerebrospinal fluid, seven HIV-infected adults underwent intensive sampling at steady-state while receiving twice-daily indinavir (800 mg) and ritonavir (100 mg). Serial cerebrospinal fluid and plasma samples were obtained at 10 time points from each subject. Free indinavir accounted for 98.6% of drug in cerebrospinal fluid and 55.9% in plasma. Mean cerebrospinal fluid C max , C min , and area under the concentration-time curve from 0 to 12 h (AUC 0-12 ) values for free indinavir were 735 nM, 280 nM, and 6,502 nM h −1 , respectively, and the free levels exceeded 100 nM in every sample. The cerebrospinal fluid/plasma AUC 0-12 ratio for free indinavir was 17.5% ± 6.4%. This ratio was remarkably similar to results obtained in a previous study in which subjects received indinavir without ritonavir, indicating that ritonavir did not have a substantial direct effect on the barrier to indinavir penetration into cerebrospinal fluid. Low-dose ritonavir increases cerebrospinal fluid indinavir concentrations substantially more than 800 mg of indinavir given thrice daily without concomitant ritonavir, despite a lower total daily indinavir dose." @default.
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• W2146027341 date "2003-07-01" @default.
• W2146027341 modified "2023-10-16" @default.
• W2146027341 title "Effects of Ritonavir on Indinavir Pharmacokinetics in Cerebrospinal Fluid and Plasma" @default.
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• W2146027341 doi "https://doi.org/10.1128/aac.47.7.2131-2137.2003" @default.
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