Pharmacokinetic and Statistical Analyses

Pharmacokinetic parameters of upadacitinib were estimated by noncompartmental methods using SAS Version 9.3 (SAS Institute, Inc., Cary, North Carolina) and included the C_max and the time to C_max (peak time, T_max), terminal phase elimination half‐life (t_1/2), AUC from time 0 to the time of the last measurable concentration (AUC_t) or to infinity (AUC_∞), and apparent oral clearance value (CL/F, where F is the bioavailability). The percentage of upadacitinib dose eliminated unchanged in urine was calculated as the amount of upadacitinib recovered in urine divided by the administered dose and multiplied by 100. Renal clearance was calculated as the amount of upadacitinib eliminated in urine divided by AUC_∞.

To assess the effect of renal impairment on upadacitinib plasma exposures, a regression analysis was performed on the logarithms of C_max, AUC_t, and AUC_inf against the eGFR and creatinine clearance, with eGFR as the parameter of primary interest. The 90%CIs were provided for the ratios of the predicted C_max, AUC_t, and AUC_inf values by using the mean value from each impaired group to that from the normal group. In addition, an analysis of covariance (ANCOVA) was performed for C_max, AUC_t, and AUC_inf, CL/F, T_max, and β. Body weight, sex, and age were considered as possible covariates (P < .10) in both the regression and ANCOVA analyses. Within the framework of the ANCOVA, the effect of renal impairment was estimated for each group and compared to the normal group (P < .05). For AUC_t, AUC_inf, and C_max, 90%CIs were provided for the ratio of the central value of each impaired group to that of the normal group.