Determination of drug concentrations and dose proportionality
Plasma and urine PK parameters of KCL‐286 were analysed using noncompartmental analysis. Actual dosing and PK sampling times were used for PK parameters. Linear log trapezoidal method (linear on ascending and log on descending concentrations) was used to integrate the plasma concentration time profiles out to the time that the last measurable concentration. Parameters included, AUC, area under the plasma concentration–time curve; AUC (Dose proportionality was assessed using a power model which was fitted by restricted maximum likelihood using SAS Proc Mixed. The intercept and slope were fitted as fixed effects based on the assumption of linearity. An estimate of the slope was obtained from the power model along with its 2‐sided 90 and 95% CI. Exposure was deemed dose‐proportional if it was within 2‐fold of the mean.