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How is antiviral efficacy measured10,11
The IC value
IC50: the in vitro concentration of drug required to inhibit viral replication by 50%
IC90: the in vitro concentration of drug required to inhibit viral replication by 90%
IC50 and IC90 vary depending on a number of factors, including the viral strain, cell type and assay used, and on adjustments made for plasma protein binding.12 For any one PI, there is therefore a range of IC values5,13-16 (Table 1), even for wild-type virus
| PI |
IC50* (nM) |
IC90* or IC95* (nM) |
EC50 (nM, based on Cmin) |
| Saquinavir16,17 |
1�30 |
5�80 |
75 |
|
Indinavir13,18 |
NA |
25�100 |
41 |
| Ritonavir19,20 |
4�153 |
105 |
NA |
| Nelfinavir14 |
NA |
7�196 |
NA |
| Amprenavir15,21 |
80�410 |
NA |
172 |
| Lopinavir5 |
4�289 |
NA |
NA |
Table 1. Inhibitory and effective concentrations for the PIs (NA - not available. *Require further adjustment for protein binding. **Does not require further adjustment for protein binding)
- Drug-resistant viral strains have higher IC50 or IC90 values compared with wild-type viral strains, as illustrated in Figures 4a and 4b
Figures 4a and 4b. In vitro antiviral potency � effect of resistance.
The EC value
In clinical practice, in vivo effective concentrations (ECs) may be more accurate reflections of the levels of drug required to achieve viral suppression. The EC is a direct in vivo measure of drug potency and therefore, unlike in vitro IC estimates, this value does not require adjustment for protein binding. It represents the plasma concentration of drug required to produce a specific percentage of suppression of maximal HIV RNA replication.
- The EC can be derived based on a number of pharmacokinetic parameters, most frequently Cmin or AUC17,18,21
- The EC50 (Cmin) of saquinavir in antiretroviral naive patients is 50 ng/ml17
(75 nM; Table 1), based on an analysis of 74 patients treated with saquinavir monotherapy. This was the concentration of saquinavir that led to a 1 log (50% of maximal) reduction in plasma HIV-1 RNA concentration in these patients. EC values have also been presented for amprenavir21 and indinavir18 (Table 1) |
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