Original Paper

Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats

  1. Anasuya Hazra1,†,
  2. Nancy Pyszczynski1,
  3. Debra C. DuBois1,2,
  4. Richard R. Almon1,2,
  5. William J. Jusko1,*

Article first published online: 14 JUN 2007

DOI: 10.1002/bdd.551

Issue

Biopharmaceutics & Drug Disposition

Biopharmaceutics & Drug Disposition

Volume 28, Issue 6, pages 263–273, September 2007

Additional Information

How to Cite

Hazra, A., Pyszczynski, N., DuBois, D. C., Almon, R. R. and Jusko, W. J. (2007), Pharmacokinetics of methylprednisolone after intravenous and intramuscular administration in rats. Biopharm. Drug Dispos., 28: 263–273. doi: 10.1002/bdd.551

Author Information

  1. 1

    Department of Pharmaceutical Sciences, University at Buffalo, State University of NY, Buffalo, NY 14260, USA

  2. 2

    Department of Biological Sciences, University at Buffalo, State University of NY, Buffalo, NY 14260, USA

  1. †

    Clinical Pharmacology, Pfizer, Inc., Groton, CT 06340, USA

*565 Hochstetter Hall, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA

Publication History

  1. Issue published online: 18 JUN 2007
  2. Article first published online: 14 JUN 2007
  3. Manuscript Accepted: 23 JAN 2007
  4. Manuscript Revised: 14 JAN 2007
  5. Manuscript Received: 27 OCT 2006

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Keywords:

  • methylprednisolone;
  • corticosteroids;
  • pharmacokinetics;
  • intramuscular injection;
  • tyrosine aminotransferase

Abstract

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.

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