| Autor: |
Haas, David W., Johnson, Benjamin, Nicotera, Janet, Bailey, Vicki L., Harris, Victoria L., Bowles, Farideh B., Raffanti, Stephen, Schranz, Jennifer, Finn, Tyler S., Saah, Alfred J., Stone, Julie |
| Zdroj: |
Antimicrobial Agents and Chemotherapy; July 2003, Vol. 47 Issue: 7 p2131-2137, 7p |
| Abstrakt: |
ABSTRACTTherapeutic 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 Cmax, Cmin, and area under the concentration-time curve from 0 to 12 h (AUC0-12) 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 AUC0-12ratio 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. |
| Databáze: |
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