Pharmacokinetics and anti-inflammatory pharmacodynamics of prednisolone in cynomolgus monkey.
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-alpha, IL-1beta, IL-6 and IL-8 with very similar IC50 estimates from 0.09 to 0.16 microg ml(-1) (from 0.24 to 0.44 microM). The monkey demonstrated a similar pharmacokinetics-pharmacodynamics profile of prednisolone when compared with man (from the literature).
Zheng
Y J
YJ
Pfizer Global Research & Development, St. Louis Laboratories, Chesterfield, MO 63017, USA.
Hawk
M
M
Yuan
H
H
Hope
H R
HR
Baratta
M
M
Zutshi
A
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006207:Half-Life; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D008297:Male; D008657:Metabolic Clearance Rate; D011239:Prednisolone / Q000493:pharmacokinetics* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D011239:Prednisolone