Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass.
Published
Journal Article
Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)-induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)-6 and IL-10 concentrations from neonates enrolled in a randomized trial comparing one vs. two doses of methylprednisolone to develop indirect response population pharmacokinetic/pharmacodynamic models characterizing the exposure-response relationships. We applied the models to simulate methylprednisolone dosages resulting in the desired IL-6 and -10 exposures, known mediators of CPB-induced inflammation. A total of 64 neonates (median weight 3.2 kg, range 2.2-4.3) contributed 290 plasma methylprednisolone concentrations (range 1.07-12,700 ng/mL) and IL-6 (0-681 pg/mL) and IL-10 (0.1-1125 pg/mL). Methylprednisolone plasma exposure following a single 10 mg/kg intravenous dose inhibited IL-6 and stimulated IL-10 production when compared with placebo. Higher (30 mg/kg) or more frequent (twice) dosing did not confer additional benefit. Clinical efficacy studies are needed to evaluate the effect of optimized dosing on outcomes.
Full Text
Duke Authors
Cited Authors
- Hornik, CP; Gonzalez, D; Dumond, J; Wu, H; Graham, EM; Hill, KD; Cohen-Wolkowiez, M
Published Date
- December 2019
Published In
Volume / Issue
- 8 / 12
Start / End Page
- 913 - 922
PubMed ID
- 31646767
Pubmed Central ID
- 31646767
Electronic International Standard Serial Number (EISSN)
- 2163-8306
Digital Object Identifier (DOI)
- 10.1002/psp4.12470
Language
- eng
Conference Location
- United States