International Workshop on
More on SQV+RTV Once Daily PK and Body Weight May Influence Drug Blood Levels
At the recent Pharmacology Workshop there were a number of reports on once daily SQV+RTV (1600mg/100mg). You should have received an email of these reports today from NATAP. For future reference the reports are archived on NATAP web site.
Fortovase Cmin Ed Acosta reported at the Wksp that in a previous study in healthy volunteers, trough at 24 hrs was 5.5-fold in 1600/100 once daily vs standard SQV 1200 3x/daily. In the study reported at the Wksp in HIV-infected the median 24 hr trough level was 376 ng/mL for all 49 patients in study and 429 for 6 patients in PK substudy. They also report finding for these 6 patients that Cmax was 6,435 ng/mL, AUC-24 was 66,920, and C24h was 429. In the Roche press announcement issued today April 19, they report that from a few previous trials Fortovase Cmin was 200 ng/mL. And the EC50 of Fortovase is 50 ng/mL.
Cmin in Women The press announcement also reports that previously reported was that among 15 women (501 ng/mL) in the study described above higher median Cmin concentrations of SQV were seen compared to the 34 men (354 ng/mL) in the study. But this difference was not statistically significant. Still, taken with data from other studies there may be a point here. The Abbott group found body weight was associated with Lopinavir blood levels, but not with gender. The Burger group from the Netherlands found higher indinavir levels in 10%-20% of women, but the median was about the same comparing men to women. And Burger reported higher likelihood of experiencing toxicities when blood levels were higher in the women. However, Burger did not look at body weight. Taken together the data suggests that body weight could be the reason for higher blood levels and possibly not female gender, but we don't know for sure.