|
APTIVUS®(二十八)
|
uarr; |
0.78 (0.72, 0.84) |
2.33 (2.02, 2.69) |
- |
|
|
10 mg
(1 dose) |
500/200 mg BID
(17 doses) |
17 |
↔ |
0.70 (0.63, 0.78) |
1.01 (0.83, 1.21) |
- |
|
Tenofovir |
300 mg
(1 dose) |
500/100 mg BID
750/200 mg BID
(23 doses) |
22
20 |
↓
↓ |
0.77 (0.68, 0.87)
0.62 (0.54, 0.71) |
0.98 (0.91, 1.05)
1.02 (0.94, 1.10) |
1.07 (0.98, 1.17)
1.14 (1.01, 1.27) |
|
Zidovudinec |
300 mg BID
300 mg BID
300 mg BID
(43 doses) |
250/200 mg BID
750/100 mg BID
1250/100 mg BID
(42 doses) |
48
31
23 |
↓
↓
↓ |
0.54 (0.47, 0.62)
0.51 (0.44, 0.60)
0.49 (0.40, 0.59) |
0.58 (0.51, 0.66)
0.64 (0.55, 0.75)
0.69 (0.49, 0.97) |
-
-
- |
|
|
300 mg
(1 dose) |
500/100 mg BID
750/200 mg BID
(23 doses) |
29
25 |
↓
↔ |
0.39 (0.33, 0.45)
0.44 (0.36, 0.54) |
0.57 (0.52, 0.63)
0.67 (0.62, 0.73) |
0.89 (0.81, 0.99)
1.25 (1.08, 1.44) |
|
Zidovudine glucuronide |
|
500/100 mg BID
750/200 mg BID
(23 doses) |
29
25 |
↑
↑ |
0.82 (0.74, 0.90)
0.82 (0.73, 0.92) |
1.02 (0.97, 1.06)
1.09 (1.05, 1.14) |
1.52 (1.34, 1.71)
1.94 (1.62, 2.31) |
12.4 Microbiology
Mechanism of Action
Tipranavir (TPV) is an HIV-1 protease inhibitor that inhibits the virus-specific processing of the viral Gag and Gag-Pol polyproteins in HIV-1 infected cells, thus preventing formation of mature virions.
Antiviral Activity
Tipranavir inhibits the replication of laboratory strains of HIV-1 and clinical isolates in acute models of T-cell infection, with 50% effective concentrations (EC50) ranging from 0.03 to 0.07 μM (18-42 ng/mL). Tipranavir demonstrates antiviral activity in cell culture against a broad panel of HIV-1 group M non-clade B isolates (A, C, D, F, G, H, CRF01 AE, CRF02 AG, CRF12 BF). Group O and HIV-2 isolates have reduced susceptibility in cell culture to tipranavir with EC50 values ranging from 0.164 -1 μM and 0.233-0.522 μM, respectively. When used with other antiretroviral agents in cell culture, the combination of tipranavir was additive to antagonistic with other protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir) and generally additive with the NNRTIs (delavirdine, efavirenz, and nevirapine) and the NRTIs (abacavir, didanosine, emtricitabine, lamivudine, stavudine, tenofovir, and zidovudine). Tipranavir was synergistic with the HIV-1 fusion inhibitor enfuvirtide. There was no antagonism of the cell culture combinations of tipranavir with either adefovir or ribavirin, used in the treatment of viral hepatitis.
Resistance
In cell culture:
HIV-1 isolates with a decreased susceptibility to tipranavir have been selected in cell culture and obtained from patients trea |
