Effects of Gender, Race, Age & Weight on Pkarmacokinetics of Lopinavir after a Single Dose of Kaletra in Healthy Adults

Rick Bertz from Abbott reported PK data from an analysis of 7 single-dose Kaletra bioavailability studies in healthy adults. Gender, race, age, and body weight were factors considered. A dose of 400/100 or 400/200 Kaletra (lopinavir/ritonavir) was taken with food. Data from 194 subjects were analyzed (50 female, 144 male). 157 were Caucasian and 17 Hispanic and 20 Black. Age ranged from 18-55 (31 mean age). Weight range was 54 to 100 kg (mean 75 kg).

RESULTS
Weight had a statistically significant effect on drug blood levels (AUC and Cmax), but not on t-1/2. Subjects with lower body weight tended to have higher lopinavir Cmax (peak drug levels in blood) and AUC (total drug blood levels during dosing period). Although Bertz did not study this, higher drug blood levels may be associated with more drug-related toxicities. About a 20% increase in AUC would be predicted for a 25% decrease in body weight. The question is how much actual affect in fact this would have on a person. A 20% increase in AUC may not be clinically relevant in some situations, but is it relevant to an increase in toxicities? Or if a 10% increase in AUC occurs, will that actually cause an increase in toxicities or the severity of toxicities?

Blacks had slightly lower lopinavir AUC (-14%) and Cmax (-14%) than caucasians. Bertz concluded that these differences are probably not clinically relevant as reflected by similar efficacy results for Blacks & Caucasians in the large phase 3 study (study #863). Bertz concluded that body weight was the most significant predictor of lopinavir PK after single doses in healthy adults. But, again the clinical relevance remains to be determined.

In a study reported by David Burger at this Workshop he reports 10%-20% of women experience higher indinavir blood levels which may be associated with toxicities. But, I don't think Burger looked at body weight as a possible explanation.