Women May Have Different Indinavir Blood Levels

Reported by Jules Levin

This is a preliminary review of abstract 4.2--"Pharmacokinetc variability caused by gender: do women have higher indinavir exposure than men?" authored by David Burger and colleagues at the University Medical Centre Nijmegen, the Netherlands.

They have accumulated a database because they offer in house TDM for doctors. So they analyzed samples from females taking IDV regimens 800 mg every 8 hours. They compared their findings of IDV blood levels to those from a control group of men. They compared the blood levels to a level considered optimal from a group of 14 (12 male, 2 female) and they called this optimal level the IDV concentration ratio (CR). In abstract 6.6 Burger reports that "IDV CR calculated in samples drawn between 1 and 6 hours post ingestion can be used to estimate the AUC in patients using IDV 800mg tid". In this poster Burger discusses how he validates his CR.

In the original study (4.2 abstract), Burger used 227 samples from women patients and the median CR of IDV was 1.18 Interquartile range 0.65-1.89) with 58% having an IDV CR>1.00. The median CR in 61 samples in men was 0.96 (interquartile range 0.60-1.70), with 47% having a CR level >1.00. . So, the IDV levels were slightly higher in men but the authors said it was not statistically significant. "Intoxication" was noted as an indication for the doctor requesting TDM in 17% of the females and 6.6% of the men. A dose reduction of IDV to 600 or 400 mg every 8 hrs was applied in 9.7% of women (vs. 1.1% of the men) after they had reported IDV related side effects and TDM was performed. Burger concluded that the data indicate that women as a group have roughly similar pharmacokinetic exposure to IDV when compared to men. However, a subgroup of 10%-20% of the women may have substantially elevated plasma concentrations, leading to a higher incidence of toxicities and subsequent dose reductions. Burger said he was unsure of the reasons for these gender differences. I would speculate that they could be due to weight or real gender differences in metabolism.

This data suggests to me that we need to follow-up with additional studies of HIV drug dosing & toxicities in women and as it may relate to weight.