02% increase in LPV FU. Albumin was not significantly correlated with LPV FU for either of the pharmacokinetic study days. Women receiving high dose LPV/r (533/133) did learn more not have significantly different LPV FU compared to women receiving standard dose LPV/r (400/100). Likewise, the time that elapsed before PP evaluations did not appear to have an effect on LPV FU when comparing measurements ≤4 weeks to those >4 weeks PP, a break-point near the median time for PP visits (3.4 weeks) (data not shown). The antiviral effect of LPV depends on multiple factors that extend beyond the pharmacokinetics of total

or unbound drug. These factors include processes affecting the penetration of drug into target cells and tissues (e.g. transport proteins) and how susceptible the virus is to the ARV. A primary goal of pharmacokinetic studies is to measure active drug as close to the site of pharmacological activity as is possible. Therefore PK studies that measure the percentage unbound (FU) of highly bound drugs (i.e. the fraction that is pharmacologically active and free to AZD1208 mw traverse membranes) may help investigators get one step closer to achieving this goal. However, it remains unclear if unbound drug exposure in plasma alone is a strong predictor of active drug

exposure within cells and target tissues. The pharmacokinetic exposure of LPV as estimated through the AUC of total drug is reduced 28% with standard LPV/r SGC dosing during pregnancy as previously reported. In addition, the 12 h trough concentration, a measurement sometimes employed in clinical practice, is Tobramycin reduced 56% during pregnancy [4]. Eighty percent of these women had pharmacokinetic parameters below the target 10th percentile of nonpregnant women in late pregnancy leading to the study of a second cohort of women receiving an increased dose of LPV 533/RTV 133 mg twice daily. Eighty-one percent (81%) of women

receiving the increased dose had AUC estimates exceeding the target 10th percentile during third-trimester pregnancy [5]. To further characterize the effect of pregnancy on LPV pharmacokinetics we determined changes in the plasma proteins albumin and AAG and the LPV FU in nearly all women who had undergone pharmacokinetic analysis and for whom sufficient sample was available [4,5]. We observed decreases in AAG and albumin concentrations and an increase in LPV FU during pregnancy. The increase in LPV FU averaged 18%, which may partially mitigate a reduction in total LPV concentrations observed with standard dosing [4]. These data are consistent with a recent report in 10 HIV-infected women where LPV FU was altered by 38% [6].