|
|
1125 mg q8h for 7 days |
15 |
↓ |
0.76
(0.68; 0.85) |
0.82
(0.74; 0.90) |
0.90
(0.81; 1.01) |
|
600 mg EFV /300 mg TDF qd for 7 days |
1500 mg q12h for 7 days |
16 |
↓ |
0.80
(0.74; 0.86) |
0.85
(0.79; 0.91) |
0.89
(0.82; 0.96) |
|
Fosamprenavir (fAPV), boosted with ritonavir (rtv) |
700 mg fAPV/ 100 mg bid rtv for 20 days |
750 mg q8h for 10 days |
18 |
↓ |
0.65
(0.59; 0.70) |
0.53
(0.49; 0.58) |
0.44
(0.40; 0.50) |
|
700 mg fAPV/ 100 mg bid rtv for 24 days |
1125 mg q12h for 4 days |
17 (N=18 for Cmin) |
↓ |
0.60
(0.55; 0.67) |
0.51
(0.47; 0.55) |
0.42
(0.37; 0.47) |
|
Lopinavir (LPV), boosted with ritonavir (rtv) |
400 mg LPV/ 100 mg rtv bid for 20 days |
750 mg q8h for 10 days |
12 |
↔ |
0.96
(0.87; 1.05) |
1.06
(0.96; 1.17) |
1.14
(0.96; 1.36) |
|
Tenofovir disoproxil fumarate |
300 mg qd for 7 days |
750 mg q8h for 7 days |
16 |
↑ |
1.30
(1.16; 1.45) |
1.30
(1.22; 1.39) |
1.41
(1.29; 1.54) |
|
Tenofovir, on co-administration of tenofovir disoproxil fumarate (TDF) and efavirenz (EFV) |
600 mg EFV /300 mg TDF qd for 7 days |
1125 mg q8h for 7 days |
15 |
↑ |
1.22
(1.12; 1.33) |
1.10
(1.03; 1.18) |
1.17
(1.06; 1.28) |
|
600 mg EFV /300 mg TDF qd for 7 days |
1500 mg q12h for 7 days |
16 |
↑ |
1.24
(1.13; 1.37) |
1.10
(1.03; 1.17) |
1.06
(0.98; 1.15) |
12.4Microbiology
Mechanism of Action
Telaprevir is an inhibitor of the HCV NS3/4A serine protease, necessary for the proteolytic cleavage of the HCV encoded polyprotein into mature forms of the NS4A, NS4B, NS5A and NS5B proteins and essential for viral replication. In a biochemical assay, telaprevir inhibited the proteolytic activity of the recombinant HCV NS3 protease domain with an IC50 value of 10 nM.
Antiviral Activity in Cell Culture
In an HCV subtype 1b replicon assay, the telaprevir EC50 value against wild-type HCV was 354 nM in a 2-day cell culture assay, and in a subtype 1a infectious virus assay, the EC50 value was 280 nM in a 5-day cell culture assay. In biochemic
