Pharmacokinetics and anti-inflammatory pharmacodynamics of prednisolone in cynomolgus monkey

Abstract

The purpose was to investigate whether the pharmacokinetics and pharmacodynamics of prednisolone in the non-human primate was an appropriate surrogate for man.After single intravenous doses of 0.03, 0.3, and 3 mg kg−1, prednisolone demonstrated a dose-dependent clearance and volume of distribution. When corrected for concentration-dependent protein binding, the free clearance was linear at the tested dose levels. The protein binding-corrected volume of distribution was similar across doses. The serum half-life was estimated as being between 2 and 4 h. Prednisolone exhibits near complete inhibition of the cytokines TNF-α, IL-1β, IL-6 and IL-8 with very similar IC50 estimates from 0.09 to 0.16 μg ml−1 (from 0.24 to 0.44 μM).The monkey demonstrated a similar pharmacokinetics–pharmacodynamics profile of prednisolone when compared with man (from the literature).