October 28, 2001
Saquinavir (SQV) levels can be significantly reduced when prescribed with efavirenz (EFV). In a previous pharmacokinetic (PK) study of the saquinavir and efavirenz interaction, it was found that efavirenz reduced the area under the curve (AUC) of saquinavir by 62%, while the AUC of efavirenz remained almost unchanged. However, the addition of ritonavir (RTV) appears to minimize the effect of efavirenz on saquinavir levels. In a trial by Kurowski and colleagues, which was presented as a late breaker poster at the 8th ECCATHI, the PK interaction between efavirenz and saquinavir given with "boosting" doses of ritonavir (all dosed once daily) were evaluated.
Twenty-four healthy volunteers were divided into two treatment arms. Group A received efavirenz 600mg daily for 14 days and on the 15th day added saquinavir 1,600mg and ritonavir 200mg to the daily regimen. Group B received the saquinavir/ritonavir therapy alone for 14 days and on day 15 efavirenz was added for 2 weeks. A pharmacokinetic (PK) profile was performed for each group on days 14 and 28. The PK profile of saquinavir/ritonavir alone was compared to the efavirenz/saquinavir/ritonavir PK profile.
With the addition of efavirenz, the AUC of saquinavir was reduced by 18.9% as compared with saquinavir/ritonavir alone, and the saquinavir Cmax was reduced from 2,340 ng/ml to 2,130 ng/ml, but the trough levels of saquinavir remained unchanged. None of these results were statistically or clinically significant. No raw data on the effects of efavirenz levels were reported although the authors state the "efavirenz concentrations were not significantly influenced by saquinavir."
The authors concluded, "the saquinavir trough levels remained unaffected in this trial when combined with efavirenz. The observed small differences of the AUC and the Cmax for saquinavir are not expected to limit the clinical use of this triple combination."
As we move toward once-daily therapy, pharmacokinetic studies such as this gain increasing importance. Knowing the exact interaction between medications, before we combine them in antiretroviral regimens, is crucial. The proof still lies, however, in showing that a regimen is successful in the treatment of patients and there was no data of that nature presented in this purely PK study.