The method has a calibration range of 190–1900 mg/mL. Samples with values lower than 190 mg/mL were repeated using double the amount of sample. Low, middle Compound Library and high controls (n=8 of each) showed precision and accuracy of <13.1%CV and within 3.5% deviation, respectively. Albumin was determined at the Clinical Laboratory Improvement Amendments (CLIA) certified clinical chemistry laboratories associated with the clinical study sites. The Wilcoxon signed rank test was used to compare

LPV FU and other variables measured during the third trimester of pregnancy (AP) with the corresponding PP measurements. Linear regression was used to investigate the impact on LPV FU of total drug concentration, AAG, albumin concentration, LPV dose administered and the time of PP evaluations. Generalized estimating equations were used to account for the intra-subject correlations. AP and PP evaluations were carried

out in 29 and 25 women, respectively for whom sufficient plasma was available. Of these women, all but one received the identical http://www.selleckchem.com/products/abt-199.html dose for both AP and PP study periods; 16 received the LPV/r 400/100 mg bid dose and 12 received the 533/133 mg bid dose. One subject received both LPV/r doses at differing points of the study. Table 1 summarizes subject demographic and disease characteristics obtained at the time of AP pharmacokinetic sampling. Median age was 31.4 years ranging from 18.2 to 40.9 years, with the majority of women being either black (35%) or Hispanic (45%). Median gestational age was 33.9 weeks ranging from 30.4 to 37.4 weeks, and median time of PP PK evaluation since delivery was 3.4 weeks with a range of 1.7–12.9 weeks. Table 2 presents the values and percent difference AP vs. PP for AAG concentration, albumin concentration, and LPV FU. Both AAG and albumin were significantly lower during pregnancy compared to PP (P<0.0001). LPV FU was significantly higher during pregnancy compared to PP for the 0+12 h pooled CHIR-99021 samples and the 2 through 8 h pooled samples, analyzed separately or combined average FU (for both 0+12 h and 2 through 8h pooled samples) was 18% higher AP compared to

PP (P=0.001) (Table 2). LPV FU decreased as a function of increasing AAG concentration in both the AP and PP periods (Fig. 1). At the AP pharmacokinetic evaluation, each 100 mg/L (or 0.1 mg/mL) increase in AAG was associated with a decrease in LPV FU of 0.07% (P<0.0001) and at the PP pharmacokinetic evaluation, each 100 mg/L increase in AAG was associated with a decrease of 0.05% in LPV FU (P<0.0001) after adjustment for total LPV concentrations. Total plasma LPV concentration alone was not significantly correlated with LPV FU during either the AP or PP pharmacokinetic visits. However, a higher total plasma LPV concentration PP was significantly associated with reduced LPV binding and higher FU (P<0.0001) after adjustment for AAG concentration.