Document Type
Article
Publication Date
2010
Abstract
The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and noncompartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ∼200-fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation of DMP-1 in these tissues was substantially greater than that for DMP-5. Substantial amounts of MP were regenerated from both prodrugs in the liver and spleen, with the rate of release from DMP-5 being twice as fast as that from DMP-1. However, the AUCs of MP regenerated from DMP-1 in the liver and spleen were substantially higher than those after DMP-5. In contrast, in the kidneys, the AUC of MP regenerated from DMP-5 was higher than that after DMP-1 administration. These data suggest that DMP-1 may be more suitable than DMP-5 for targeting immunosuppression to the liver and spleen.
Recommended Citation
Penugonda, Suman, Hitesh K. Agarwal, Keykavous Parang, and Reza Mehvar. "Plasma pharmacokinetics and tissue disposition of novel dextran–methylprednisolone conjugates with peptide linkers in rats." Journal of pharmaceutical sciences 99, no. 3 (2010): 1626-1637.
DOI:10.1002/jps.21934
Copyright
Wiley
Included in
Amino Acids, Peptides, and Proteins Commons, Animals Commons, Immune System Diseases Commons
Comments
This is the accepted version of the following article:
Penugonda, Suman, Hitesh K. Agarwal, Keykavous Parang, and Reza Mehvar. "Plasma pharmacokinetics and tissue disposition of novel dextran–methylprednisolone conjugates with peptide linkers in rats." Journal of pharmaceutical sciences 99, no. 3 (2010): 1626-1637.
which has been published in final form at DOI: 10.1002/jps.21934.