Proportionality was assumed if the 90 % confidence interval of the dose-normalized geometric mean ratio of AUC t was within the 80.00 to 125.00 % range. The main absorption and disposition parameters [C max (-t max-), AUC t , AUC ∞ , k e and t ½] were estimated using a non-compartmental approach with a log-linear terminal phase assumption. The trapezoidal rule was used to estimate the area under the concentration–time curve, and the terminal phase was estimated by maximizing the coefficient of determination estimated from the log-linear regression model. They were not to be estimated for AG-881 cost individual concentration–time profiles, where the terminal selleck products log-linear phase could not be reliably characterized.
Furthermore, the mean, median, minimal value, maximal value, standard deviation and coefficient of variation were calculated for plasma concentrations at each individual timepoint and for all pharmacokinetic parameters. Between-treatment comparisons were performed using the ANOVA model mentioned above for all parameters except t max, which was analyzed using a non-parametric approach. Statistical and pharmacokinetic analyses were generated using Kinetic (version 9.01), an application developed at Algorithme Pharma and SAS® (version 9, GLM procedure). 3 Results 3.1 Subject Recruitment A total of 12
healthy volunteers were included (3 male, 9 female), with a median age of 43 years (range 28, 58), weight of 66.1 kg (range N-acetylglucosamine-1-phosphate transferase 51.6, 96.3), height of 167 cm (range 157, 184) and body mass index of 24.0 kg/m2 (range 20.2, 28.4). All (100 %) INK1197 concentration subjects were white, and all of them completed the crossover design and received a single oral dose of the assigned treatment on day 1 and day 8. 3.2 Treatment Compliance All subjects took the study medication according to the protocol. The investigational product was administered under
the supervision of the qualified investigator or his designees. The film-coated tablet was to be swallowed whole and was not to be chewed or broken. Following administration of the drug, each subject’s hands and mouth were checked in order to confirm the consumption of the medication. The physician in charge remained at the clinical site for at least the first 4 h following each drug administration and remained available at all times during the entire period of the study. 3.3 Pharmacokinetic Assessments Table 1 depicts the doxylamine pharmacokinetic results: C max, t max, AUC t , AUC t normalized, AUC ∞ , AUC t :AUC ∞ , k e and t ½ for both strengths of doxylamine hydrogen succinate, and Table 2 shows the comparison results with standards for bioequivalence. Proportionality was assumed given that the 90 % confidence interval of the dose-normalized geometric mean ratio of AUC t was within the 80.00 to 125.00 % range [98.92 % (90 % CI: 92.46, 105.83)].