PMID: 11604270Oct 18, 2001Paper

Dextran-methylprednisolone succinate as a prodrug of methylprednisolone: dose-dependent pharmacokinetics in rats

International Journal of Pharmaceutics
X Zhang, Reza Mehvar

Abstract

The dose-dependency in the pharmacokinetics of a macromolecular prodrug of methylprednisolone (MP), dextran-methylprednisolone succinate (DMP), was investigated in rats. Single doses (MP equivalent) of 2.5, 5.0, 10, 20, and 30 mg/kg of DMP were administered intravenously to rats (n=5/group), and serial blood samples (0-96 h) and spleen and liver tissues (96 h) were collected. The concentrations of DMP in plasma and spleen were analyzed using a size-exclusion chromatographic method. The concentrations of DMP in the liver samples were determined by an indirect method after sequential hydrolysis by dextranase and esterase enzymes, followed by HPLC analysis of MP. The kinetics of DMP were analyzed by non-compartmental methods. The systemic clearance of DMP decreased approximately 5-fold (from 42.1+/-11.0 to 7.72+/-1.84 ml/h per kg) when the dose was increased from 2.5 to 30 mg/kg. The nonlinearity in the clearance of DMP could be adequately described by a Michaelis-Menten type elimination with a maximum velocity of elimination of 1.72 mg/h per kg and a constant of 24.9 microg/ml. Additionally, the percent of the dose of DMP found at 96 h in the liver and spleen, where the prodrug is sequestered and gradually eliminated, significant...Continue Reading

References

May 1, 1992·The Journal of Pharmacy and Pharmacology·M NishikawaH Sezaki
Sep 1, 1992·Journal of Pharmaceutical Sciences·R Mehvar, T L Shepard
Feb 1, 1991·Journal of Pharmacokinetics and Biopharmaceutics·A Bernareggi, M Rowland
Jan 1, 1989·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·R J StockR S McCuskey
Jun 1, 1989·Journal of Clinical Pharmacology·W J Jusko
Feb 1, 1980·Pharmacological Research Communications·T OshimaK Hattori
Jun 1, 1982·Journal of Pharmacokinetics and Biopharmaceutics·H Boxenbaum
Oct 1, 1994·Journal of Pharmaceutical Sciences·R MehvarJ M Reynolds
Jul 1, 1995·Journal of Pharmaceutical Sciences·R MehvarJ M Reynolds
Mar 1, 1995·Critical Reviews in Oncology/hematology·Y Takakura, M Hashida
Jun 17, 2000·Journal of Pharmaceutical and Biomedical Analysis·R MehvarD A Hoganson
Jul 8, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·R MehvarD A Hoganson
Sep 19, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·R Mehvar
Oct 6, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·R Mehvar
Apr 1, 1957·Clinica Chimica Acta; International Journal of Clinical Chemistry·E L ROSENFELD, I S LUKOMSKAYA

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Citations

Nov 9, 2007·Pharmaceutical Research·Ching-Lin ChenJiahorng Liaw
Nov 27, 2009·Journal of the Royal Society, Interface·Wiebke Ulbrich, Alf Lamprecht
Nov 11, 2008·International Journal of Nanomedicine·Jungyeon HwangThomas Schluep
Apr 19, 2019·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Pranjal TaskarSoumyajit Majumdar

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