title: [Effect of capecitabine therapy on the blood levels of antiepileptic drugs - report of two cases].
abstract: We report the cases of 2 breast cancer patients who received capecitabine(CAP)and concomitant anticonvulsant therapy with either phenytoin(PHT)or valproate(VPA)for brain metastasis. The effect of CAP on the blood levels of the 2 anticonvulsants was different and it depended on the variation in metabolism of each drug. Case 1 involved a 59-year-old woman with recurrent breast cancer. After radiation therapy for brain metastases, the patient received PHT(400mg/day)to prevent convulsions. After 5 days of PHT administration, CAP therapy was initiated, and her blood PHT levels increased to 33.8 mg/mL. Although the PHT dose was reduced to 300mg/day, the blood PHT levels markedly increased to 45.5 mg/mL 7 days after the withdrawal of CAP. Case 2 involved a 60-year-old woman with breast cancer who underwent surgery for brain metastases and subsequently received controlled-release VPA tablets(400mg/day). No remarkable change was observed in her blood VPA levels during CAP treatment or after CAP withdrawal(the blood VAP level after 7 days of treatment was, 78.4 mg/mL; after 14 days of treatment, 73.2 mg/mL; and 7 days after withdrawal, 79.7 mg/mL). CAP has been reported to inhibit nucleic acid synthesis and/or folic acid activity rather than cytochrome P450(CYP)directly. CAP had a significant effect on the blood levels of PHT, which is metabolized via the CYP pathway. However, VPA levels remained unchanged because VPA metabolism involves other pathways, such as the beta-oxidation and conjugation pathways.
authors.affiliation: Dept. of Pharmacy, National Hospital Organization.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hiromi
authors.initials: H
authors.lastname: Jotoku
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takasaki
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Ibayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Masato
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D010672:Phenytoin / Q000097:blood* / Q000627:therapeutic use; D012640:Seizures / Q000517:prevention & control; D014635:Valproic Acid / Q000097:blood* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D014635:Valproic Acid; D010672:Phenytoin; D000069287:Capecitabine; D005472:Fluorouracil