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Pharmacokinetic
Study of Human Immunodeficiency Virus Protease Inhibitors Used in
Combination with Amprenavir [Sadler BM et al. AAC 2001;45:3663]
The authors performed pharmacokinetic studies of amprenavir with
and without indinavir, nelfinavir or saquinavir (Fortovase) with
6-9 patients per group. Standard doses were used for each drug,
and results are reported here for steady-state pharmacokinetic values
for dual combinations after three weeks. The results showed that
amprenavir AUC was decreased by 32% with co-administration of Fortovase
and increased by 33% with indinavir; nelfinavir had essentially
no important effect on AUC, but increased through amprenavir levels
by 189%. With regard to the impact of amprenavir on pharmacokinetics
of the co-administered PI, there was essentially no important change
for Fortovase or nelfinavir, but indinavir AUC decreased by 38%.
The following table provides the specific observations for the AUC,
peak levels and trough levels for both amprenavir and the co-administered
PI:
| Amprenavir
- PI Combinations |
| |
Impact
on APV |
Impact
of APV on Co-PI |
| AUC
ug h/mL |
Max
ug/mL |
Min
ug/mL |
AUC |
Cmax |
Cmin |
| SQV |
-32% |
-37% |
-14% |
-19% |
+21% |
-48% |
| IDV |
+33% |
+18% |
+25% |
-38% |
-22% |
-27% |
| NFV |
+9% |
-14% |
+189% |
+15% |
+12% |
+14% |
Comment:
The authors conclude that their studies suggest that no dose adjustment
is necessary for any of these drugs when used in the combinations
tested. They also reported no deleterious effects in terms of adverse
events.
posted
11/30/2001
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