title: Pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide in plasma and urine of cancer patients treated with a 10-day continuous infusion of ifosfamide.
abstract: The cytotoxic drug ifosfamide is subject to an extensive metabolism. This study reports the results of a pharmacokinetic study of the parent drug and the two dechloroethylated metabolites in 22 patients on a 10-day continuous infusion of ifosfamide. Ifosfamide causes a substantial induction of the enzymes responsible for its metabolism, resulting in a two-fold increase of the clearance. The maximal IF concentration is reached after 24 h, after which the concentration decreases to a steady-state. The dechloro-ethylated compounds can be detected in the plasma about 8 h after the start of the infusion with plasma half-lives longer than for IF. Urinary excretion studies revealed that at least a quarter of the IF dose is excreted as inactive compounds.
authors.affiliation: Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
authors.forename: G P
authors.initials: GP
authors.lastname: Kaijser
authors.forename: H J
authors.initials: HJ
authors.lastname: Keizer
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: A
authors.initials: A
authors.lastname: Bult
authors.forename: W J
authors.initials: WJ
authors.lastname: Underberg
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D018906:Antineoplastic Agents, Alkylating; C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; C038007:dechloroethylifosfamide; D007069:Ifosfamide