This step was repeated, and the filters were then inverted and centrifuged (at 1000 g and 37 °C for 3 min) to remove excess water. Patient plasma (500 μL) was then injected and the devices centrifuged (at 1500 g and 37 °C for 60 min). The resultant ultrafiltrate (∼170 μL per sample) was retained for drug analysis. The percentage recovery of LPV using this technique was assessed using drug-free ultrafiltrate selleck chemicals llc spiked with

14C-LPV, and was [mean (standard deviation)] 69% (± 4.1%) and constant over a range of LPV concentrations (1000, 5000, 10 000 and 15 000 ng/mL); thus no correction to unbound concentrations was applied, consistent with other plasma protein-binding studies [22–27]. All demographic and clinical

characteristics are given as the median (range). LPV and RTV trough concentrations (Ctrough) are expressed in terms of the geometric mean with 95% confidence intervals (CIs). Inter-subject variation in plasma concentrations was estimated using a coefficient of variation, expressed as a percentage [%CV=(standard deviation/mean) × 100]. The fraction of unbound LPV in plasma (fu), expressed as a percentage, was determined by: fu%=(unbound Ctrough/total Ctrough) × 100. The minimum effective concentration (MEC) for LPV was defined as 1000 ng/mL [28]. In addition, a predefined cut-off for nonadherence was proposed based on data from a healthy volunteer study assessing the decline in LPV over 72 h after drug cessation selleck screening library [29]. For an LPV/r twice daily regimen, LPV plasma concentrations were approximately (geometric mean; n=16) 384 ng/mL in the case of a single missed dose (24 h post drug cessation) and<10 ng/mL following two or more missed doses

(36–48 h post drug cessation). Thus we assumed plasma concentrations of <384 ng/mL to be indicative of noncompliance and requiring further verification by study personnel and excluded these values from subsequent statistical analyses. Although there are reported differences in antiretroviral www.selleck.co.jp/products/Fludarabine(Fludara).html concentrations between healthy subjects and HIV-infected patients, no such relationship has been demonstrated for LPV/r [30], and hence in the current analysis comparison of the two populations was considered justifiable. Differences in pharmacokinetic data antepartum vs. postpartum were assessed independently using a one-way analysis of variance (anova), with a Bonferroni correction to test for multiple comparisons. Normality of data was assessed using a Shapiro–Wilk test, and non-normally distributed data were log-transformed. Additionally, patients with matched third trimester and postpartum samples were compared by means of a paired t-test. All statistics were performed and analysed using Arcus Quickstat (version 1.1©1997; Biomedical Software, Statsdirect Ltd, Cheshire, UK). P-values are two-sided at the 0.05 significance level.