Pharmacokinetics of ifosfamide, 2- and 3-dechloroethylifosfamide in plasma and urine of cancer patients treated with a 10-day continuous infusion of ifosfamide.
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.
Kaijser
G P
GP
Department of Pharmaceutical Analysis, Faculty of Pharmacy, Utrecht University, The Netherlands.
Keizer
H J
HJ
Beijnen
J H
JH
Bult
A
A
Underberg
W J
WJ
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*
D018906:Antineoplastic Agents, Alkylating; C064445:dechloroethylcyclophosphamide; D003520:Cyclophosphamide; C038007:dechloroethylifosfamide; D007069:Ifosfamide