Section 5.2 — Pharmacokinetic properties

Absorption Veraxanib is absorbed following oral administration with a median time to maximum plasma concentration (Tmax) of 2–4 hours. The absolute oral bioavailability is approximately 71%. Administration with a high-fat meal did not alter overall exposure (AUC) but delayed Tmax by approximately 1 hour; no food restriction is required (see section 4.2). Steady-state is reached within 7 days of once-daily dosing. Distribution The apparent volume of distribution at steady state is approximately 185 L. Plasma protein binding is approximately 97%, primarily to albumin. Metabolism Veraxanib is metabolised primarily by CYP3A4 to an active M1 metabolite, which accounts for approximately 15% of total exposure. In vitro, veraxanib is a weak inhibitor of CYP2D6 (Ki 18 µM). Elimination The mean elimination half-life is approximately 24 hours at steady state. The apparent oral clearance is approximately 7 L/h. Excretion is primarily faecal (72%) with renal excretion accounting for approximately 21% of the dose.