Population pharmacokinetic modeling of oral brepocitinib in healthy volunteers and patients with immuno ‐inflammatory diseases

The objective of this population pharmacokinetic (PK) analysis was to characterize the concentration –time profile of brepocitinib plasma concentration after single- and multiple-oral administration in healthy volunteers (HVs) and patients with immuno-inflammatory diseases. Blood samples from phase I HV and phase II clinical studies of patients with alopecia areata, psoriasis, psoriatic arthritis , ulcerative colitis (UC), vitiligo, and hidradenitis suppurativa were analyzed using a nonlinear mixed-effects modeling approach. Effects of patients' characteristics on brepocitinib exposure were investigated. Overall, 8552 brepocitinib plasma concentrations from 775 individuals were included in t he analysis. The PKs of brepocitinib were adequately described by a two-compartment model with first-order absorption and a lag time for tablet formulation, dose-dependent bioavailability, and Box–Cox transformed interindividual variabilities on apparent clearance (CL/F) and apparent central volum e of distribution (Vc/F). For a typical 70-kg non-Asian female patient with baseline aspartate aminotransferase of 22 unit/liter, CL/F and Vc/F estimates were 17.5 L/h and 88.5 L, respectively. Asians had a higher exposure (independent of body weight), caused by a 10% lower CL/F when compared to oth er individuals. Independent of baseline body weight, the male population showed 13% higher Vc/F compared to the female population. Patients with UC were predicted to have 46% slower absorption ra...
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Tags: ARTICLE Source Type: research