Population pharmacokinetic analysis of RO5459072, a low water-soluble drug exhibiting complex food-drug interactions.

ABSTRACT:

Aims

RO5459072, a cathepsin-S inhibitor, Biopharmaceutics Classification System class 2 and P-glycoprotein substrate, exhibited complex, nonlinear pharmacokinetics (PK) while fasted that seemed to impact both the absorption and the disposition phases. When given with food, all nonlinearities disappeared. Physiologically based PK (PBPK) modelling attributed those nonlinearities to dose-dependent solubilisation and colonic absorption. The objective of this population PK analysis was to complement the PBPK analysis.

Methods

PK profiles in 39 healthy volunteers after first oral dosing (1-600 mg) while fasted or fed in single and multiple ascending dose studies were analysed using population compartmental modelling.

Results

The PK of RO5459072 while fed was characterized b

SUBMITTER: Kratochwil NA 

PROVIDER: S-EPMC8451882 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature