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Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats
Author(s) -
Hazra Anasuya,
Pyszczynski Nancy,
DuBois Debra C.,
Almon Richard R.,
Jusko William J.
Publication year - 2007
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.551
Subject(s) - pharmacokinetics , bioavailability , pharmacology , pharmacodynamics , chemistry , dosing , methylprednisolone , absorption (acoustics) , kinetics , elimination rate constant , intramuscular injection , medicine , volume of distribution , physics , quantum mechanics , acoustics
Methylprednisolone (MPL) pharmacokinetics was examined in adrenalectomized (ADX) and normal rats to assess the feasibility of intramuscular (i.m.) dosing for use in pharmacodynamic studies. Several study phases were pursued. Parallel group studies were performed in normal and ADX rats given 50 mg/kg MPL (i.v. or i.m.) and blood samples were collected up to 6 h. Data from studies where normal rats were dosed with 50 mg/kg MPL i.m. and killed over either 6 or 96 h were combined to determine muscle site and plasma MPL concentrations. Lastly, ADX rats were dosed with 50 mg/kg MPL i.m. and killed over 18 h to assess hepatic tyrosine aminotransferase (TAT) dynamics. MPL exhibited bi‐exponential kinetics after i.v. dosing with a terminal slope of 2.1 h −1 . The i.m. drug was absorbed slowly with two first‐order absorption rate constants, 1.26 and 0.219 h −1 indicating flip‐flop kinetics with overall 50% bioavailability. The kinetics of MPL at the injection site exhibited slow, dual absorption rates. Although i.m. MPL showed lower bioavailability compared with other corticosteroids in rats, TAT dynamics revealed similar i.m. and i.v. response profiles. The more convenient intramuscular dosing can replace the i.v. route without causing marked differences in pharmacodynamics. Copyright © 2007 John Wiley & Sons, Ltd.