TABLE 1.
Activity of HIV-1 protease inhibitors against cultured P. falciparumh
| Drug |
P. falciparum IC50 (μM) for:
|
Serum concn (μM) with:
|
||||||
|---|---|---|---|---|---|---|---|---|
| Standard dosing
|
Ritonavir coadministration
|
|||||||
| HB3 | D6 | Dd2 | W2 | Cmax | Cmin | Cmax | Cmin | |
| Saquinavira | 5.6 ± 0.4 | 4.8 ± 1.2 | 4.3 ± 1.2 | 1.1 ± 0.5 | 3.7 | 0.3 | 5.5 | 0.6 |
| Ritonavirb | 4.7 ± 0.2 | 7.9 ± 1.9 | 6.9 ± 2.5 | 1.2 ± 0.5 | 15.5 | 5.1 | NA | NA |
| Indinavirc | 5.8 ± 0.9 | 15.6 ± 2.6 | 31.2 ± 9.4 | 4.1 ± 2.4 | 10.3 | 0.3 | 17.2 | 0.4 |
| Nelfinavird | 15.2 ± 0.1 | 23.0 ± 3.5 | 19.1 ± 5.5 | 6.5 ± 2.3 | 6.0 | 3.3 | NA | NA |
| Amprenavire | 51.9 ± 22.4 | 25.0 ± 8.3 | 17.4 ± 12.2 | 33.3 ± 6.6 | 15.2 | 0.6 | 14.1 | 3.8 |
| Lopinavirf | 1.4 ± 0.2 | 2.0 ± 0.4 | 2.1 ± 0.2 | 0.9 ± 0.2 | NA | NA | 15.6 | 8.8 |
| Atazanavirg | 6.8 ± 0.3 | 11.6 ± 2.5 | 7.1 ± 1.3 | 2.5 ± 1.0 | 3.3 | 0.2 | 8.7 | 1.7 |
Based on saquinavir 1,200 mg three times daily (as free base) in HIV-infected individuals and coadministered saquinavir soft gel capsule 1,000 mg/ritonavir 100 mg b.i.d. in HIV-infected individuals (Roche prescribing information) (14).
Based on ritonavir 600 mg b.i.d. in healthy and HIV-infected individuals (Abbott prescribing information).
Based on indinavir sulfate 800 mg every 8 h and coadministered indinavir 800 mg/ritonavir 100 mg b.i.d. in healthy individuals with low-fat meal (3).
Based on nelfinavir mesylate 1,250 mg b.i.d. in HIV-infected individuals; Cmin was determined prior to morning dosage (Agouron prescribing information).
Based on amprenavir 1,200 mg b.i.d. in healthy individuals and coadministered amprenavir 600 mg/ritonavir 100 mg b.i.d. in HIV-infected individuals (GlaxoSmithKline prescribing information) (7).
Based on lopinavir 400 mg/ritonavir 100 mg b.i.d. in HIV-infected individuals (Abbott prescribing information).
Based on atazanavir sulfate 400 mg once a day (q.d.) in HIV-infected subjects and coadministered atazanavir 300 mg/ritonavir 100 mg q.d. (Bristol-Myers Squibb prescribing information); serum concentrations are given as geometric means of atazanavir, as free base.
IC50 data are means ± standard deviations from four experiments. Serum concentrations are from published information. Cmax and Cmin are the mean maximum and minimum serum levels achieved under standard dosing intervals, respectively. Ritonavir-boosted serum concentrations are those achieved with coadministration with ritonavir, as indicated in the other footnotes. NA, not applicable, as these formulations are not used clinically.