Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485919 | Journal of Pharmaceutical Sciences | 2010 | 9 Pages |
Abstract
The objective of this investigation was to compare the observed biliary clearance (CLb) and % of dose excreted in the bile (PDb) of mitoxantrone with the predicted values obtained from quantitative structure pharmacokinetic relationship (QSPKR) models. Blood and bile samples were collected from bile duct cannulated rats after an intravenous bolus dose of 0.5 or 2âmg/kg mitoxantrone, and the concentrations were measured by HPLC. Mitoxantrone plasma concentrations exhibited a triâexponential profile with systemic clearance of 118â±â6.8âmL/min/kg. After dosing, 6.08â±â2.32% and 5.69â±â0.59% of the dose were excreted into bile in unchanged form after a 3âh collection. CLb was 7.20â±â4.54 and 7.46â±â0.62âmL/min/kg after the two doses. With the coâadministration of 10âmg/kg GFâ120918, a Pâglycoprotein and BCRP inhibitor, PDb was reduced to 0.69â±â0.07%, suggesting that BCRP or Pâglycoprotein may play an important role in the biliary elimination of mitoxantrone. Using QSPKR models developed for the biliary excretion of cations/neutral compounds in rats, CLb and PDb of mitoxantrone were predicted as 5.18âmL/min/kg and 7.21%, respectively, suggesting that the models could be used to predict the biliary excretion of mitoxantrone. © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2502-2510, 2010
Keywords
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Authors
Xinning Yang, Marilyn E. Morris,