title: The pharmacokinetics and metabolism of ifosfamide during bolus and infusional administration: a randomized cross-over study.
abstract: In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21-day cycles, which alternated between 3 g m(-2) x (2 or 3) days given as a 1-h bolus doses, or the same total dose as a continuous infusion. Patients who received four or more cycles also alternated between two cycles on dexamethasone 4 mg 8 hourly for 3 days starting 8 h before IFOS, and two cycles off dexamethasone. A total of 34 patient cycles were studied and serum and urinary levels of IFOS, 2 dechloroethylifosfamide (2DC), 3 dechloroethylifosfamide (3DC), carboxyifosfamide (CX) and isophosphoramide mustard (IPM) were measured by thin-layer chromatography. No significant differences could be detected in the areas under the curve (AUCs) of serum concentration, nor in the proportion of IFOS or its metabolites found in the urine. There was no significant effect of dexamethasone on IFOS metabolism. These results indicate that there is no identifiable pharmacokinetic basis for insistence on either bolus or infusional methods of IFOS administration.
authors.affiliation: Department of Oncology, University College, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: Singer
authors.forename: J M
authors.initials: JM
authors.lastname: Hartley
authors.forename: C
authors.initials: C
authors.lastname: Brennan
authors.forename: P W
authors.initials: PW
authors.lastname: Nicholson
authors.forename: R L
authors.initials: RL
authors.lastname: Souhami
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001711:Biotransformation; D018592:Cross-Over Studies; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use* / Q000652:urine; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010752:Phosphoramide Mustards / Q000097:blood / Q000652:urine; D012509:Sarcoma / Q000188:drug therapy*; D012512:Sarcoma, Ewing / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D010752:Phosphoramide Mustards; C064445:dechloroethylcyclophosphamide; C064446:carboxyifosfamide; C027061:isophosphamide mustard; D003907:Dexamethasone; D003520:Cyclophosphamide; C038007:dechloroethylifosfamide; D007069:Ifosfamide