for each treatment, from plasma concentration time profiles using standard noncompartmental methods with eNCA, a validated Pfizerdeveloped PK software package. Pharmacokinetic assessments luded Sunitinib the area under the plasma concentration time profile from time zero to the end of the dosing interval , maximum plasma concentration , concentration observed at 24 h postdose , concentration observed at 12 h postdose , and time to maximum plasma concentration . Safety. Safety was evaluated in both studies by assessment of clinical laboratory tests and physical examinations, luding vital signs and electrocardiogram, at screening and at various points during each study. Adverse events and serious AEs were monitored and recorded throughout each study. Sample size calculation.
In study 1, for estimating the effect on pharmacokinetics of lersivirine, a sample size of 18 subjects was required to provide 90% confidence intervals for the difference between treatments of Androgen Receptor Antagonists the natural log scale for AUCtau and Cmax, respectively, with 90% coverage probability. For estimating the effect on the pharmacokinetics of raltegravir, a sample size of 18 subjects was required to provide 90% CIs for the difference between treatments of on the natural log scale for AUC12 and Cmax, respectively, with 90% coverage probability. In study 2 , a sample size of 12 subjects was required to provide 90% CIs for the difference between treatments of
on the natural log scale for maraviroc AUCtau and Cmax, respectively, with 80% coverage probability.
Data analysis. For all studies, the natural log AUCtau and Cmax , C24 , and C12 values were analyzed separately for each compound in each study using a mixed effect model with sequence, period, and symbols treatment as fixed effects and subject within sequence as a random effect using SAS software package 8.2 . Estimates of the adjusted mean differences and corresponding 90% CIs were obtained from the model. Exponentiation was applied to the adjusted mean differences and 90% CIs for the differences to provide estimates of the ratio of adjusted geometric means and 90% CIs for the ratios. In study 1, for the lersivirine comparison, lersivirine plus raltegravir was the test treatment and lersivirine alone was the reference treatment.
For the raltegravir comparison, raltegravir plus lersivirine was the test treatment and raltegravir alone was the reference treatment. In study 2, maraviroc plus lersivirine was the test treatment and maraviroc alone was the reference treatment. RESULTS Subjects. In total, 18 subjects participated in study 1 and 14 subjects participated in study 2. None of the subjects had presenting conditions or medical histories that were considered sufficient to affect the conduct of the study or to represent a potential risk to the subject during study participation. Subject demographics and baseline characteristics are shown in Table 2. Two subjects discontinued study 1 due to AEs while receiving lersivirine 1,000 mgQDand raltegravir 400 mg BID during period 1 of the study. Pharmacokinetics. Study 1: lersivirine and raltegravir. When administered in the presence of raltegravir at steady state,Coadministration of lersivirine with raltegravir or maraviroc was generally.