There were no significant
differences in terms of the LPV fu% (P=0.234). One patient (9%) in the first/second trimester selleck compound library and eight patients (19%) in the third trimester had undetectable (<5 ng/mL) unbound LPV concentrations (undetectable=excluded). However, the majority of these individuals had correspondingly low (<1000 ng/mL) total LPV levels. In a paired analysis of 12 patients with matched second/third trimester and postpartum samples, geometric mean total LPV concentrations were significantly (∼29%) reduced antepartum compared with postpartum (P=0.021) (Table 3), as were total RTV plasma concentrations. These patients also had measurements taken in the first (n=3) and/or second R428 (n=5) trimesters, respectively, as shown in Figure 1. One patient had a missing third trimester value as she delivered prematurely
(at 27 weeks), and therefore her TDM in the second trimester (22 weeks) was compared with her postpartum TDM. Nine of the 12 patients (75%) experienced an increase in LPV Ctrough postpartum (Fig. 1). Of the three patients with a decreased LPV Ctrough postpartum, one had previously received an LPV/r dose increase in the third trimester but reverted back to two tablets twice daily post-delivery. The remaining two patients had suspected compliance issues. One patient reported missing her night-time dose approximately once a week and the other had a history of noncompliance (she had been noncompliant in a previous pregnancy and had delivered an HIV-positive child), but in this study her records stated that she was fully compliant. The timing of pharmacokinetic sampling in these patients (both time post-dose and weeks postpartum) was consistent with that of other study participants. There were no significant differences in absolute LPV unbound Bumetanide concentrations (P=0.081) and fu% (P=0.537) at the third trimester vs. postpartum. In the present study, LPV (total and unbound) trough concentrations were determined sequentially during
pregnancy and at postpartum in women receiving the LPV/r tablet formulation at standard (400/100 mg twice daily) dosing. We observed that total LPV and RTV trough concentrations [geometric mean (95% CI)] were reduced in the third (and second) trimester(s) of pregnancy, in relation to corresponding concentrations postpartum. These data are consistent with previous reports on the LPV/r SGC (400/100 mg twice daily) in pregnancy. Furthermore, in a paired analysis of 12 patients, nine experienced an increase in LPV Ctrough at the time of postpartum sampling (Fig. 1), suggesting that plasma concentrations had normalized by approximately a median (range) of 8 (5–12) weeks postpartum. The clinical significance of decreased LPV concentrations during pregnancy is uncertain.