PHENYTOIN-INDUCED ALTERATION IN THE N-DECHLOROETHYLATION OF IFOSFAMIDE STEREOISOMERS

Citation
Mp. Ducharme et al., PHENYTOIN-INDUCED ALTERATION IN THE N-DECHLOROETHYLATION OF IFOSFAMIDE STEREOISOMERS, Cancer chemotherapy and pharmacology, 40(6), 1997, pp. 531-533
Citations number
6
Categorie Soggetti
Pharmacology & Pharmacy",Oncology
ISSN journal
03445704
Volume
40
Issue
6
Year of publication
1997
Pages
531 - 533
Database
ISI
SICI code
0344-5704(1997)40:6<531:PAITNO>2.0.ZU;2-1
Abstract
Case: A suspected alteration in ifosfamide (IFF) metabolism and pharma cokinetics was observed in a pediatric patient receiving phenytoin. Me thods: Sequential plasma samples were obtained and analyzed for the co ncentrations of the enantiomers of IFF and their N-dechloroethylated m etabolites (DCE-IFF) using a validated enantio selective gas chromatog raphic-mass spectrometic method. Results: In the phenytoin-treated pat ient, the metabolic formation of IFF enantiomers was increased and the metabolic pattern of the N-dechloroethylation altered from nonphenyto in-treated patients: (R)-3-DCE IFF much greater than(S)-3-DCE-IFF = (S )-2-DCE-IFF>(R)-2-DCE-IFF (control) vs (S)-3-DCE-IFF = (S)-2-DCE-IFF>( R)-3-DCE-IFF much greater than(R)-2-DCE-IFF (patient). Conclusions: Pr evious studies have attributed the production of the (S)-2-DCE-IFF and (S)-3-DCE-IFF metabolites to the activity of CYP2B6 and (R)-2-DCE-IFF and (R)-3-DCE-IFF to the activity of CYP3A4. The results suggest that phenytoin induced the activity of CYP2B6 to a greater extent than CYP 3A4. In addition, the patient, who was at least partially refractory t o several other treatments, went into remission after IFF treatment su ggesting that phenytoin pretreatment might increase IFF therapeutic ef ficacy.