Stereoselective pharmacokinetics of ifosfamide and its 2- and 3-N-dechloroethylated metabolites in female cancer patients

Cancer Chemotherapy and Pharmacology
C P GranvilI W Wainer

Abstract

The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m2) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480 +/- 200 vs 1960 +/- 150 microM.h). The terminal half-lives (7.57 +/- 0.99 h) and mean residence times (11.17 +/- 1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03 +/- 0.82 h and 9.37 +/- 0.88 h, respectively. The mean volume of distribution at steady rate of (R)-IFF (25.68 +/- 0.80 l/m2) was slightly smaller than that of (S)-IFF (27.35 +/- 0.89 l/m2). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20 +/- 2.70 vs 41.40 +/- 3.55 ml/m2 per min) as was total clearance (41.52 +/- 2.90 vs 52.37 +/- 3.75 ml/m(2) per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for...Continue Reading

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Citations

May 6, 2005·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Katarina AleksaGideon Koren
Dec 22, 1999·Pharmacotherapy·J I McVay, A M Wood
Mar 10, 2001·Clinical Pharmacokinetics·T KerbuschJ H Beijnen
Jul 21, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H LuP A Philip
May 8, 2010·Expert Opinion on Drug Metabolism & Toxicology·Bérénice GiraudAngelo Paci
Apr 13, 2007·Expert Opinion on Drug Metabolism & Toxicology·Hong Lu
Dec 23, 2004·The Journal of Laboratory and Clinical Medicine·Katarina AleksaGideon Koren
Mar 17, 1999·Journal of Chemotherapy·C ZolezziA Pizzoferrato
Jul 27, 2006·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H LuK K Chan

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