title: Pharmacokinetic interaction between high-dose methotrexate and oxacillin.
abstract: An 18-year-old man received two high-dose methotrexate cycles for the treatment of an osteosarcoma. Fifteen grams of methotrexate were infused over 6 hours. During the second cycle, co-administration of oxacillin (1g/8h) resulted in prolonged and marked elevation of methotrexate plasma concentrations. The patient experienced acute toxicity with renal failure, myelosuppression, mucitis, fever, and dermatologic abnormalities. After an initial improvement with folinic acid rescue and hemodialysis, the patient died. Oxacillin may thus inhibit the elimination of methotrexate.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, Pellegrin Hospital and University Victor Ségalen, Bordeaux, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Titier
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lagrange
authors.forename: Fabienne
authors.initials: F
authors.lastname: Péhourcq
authors.forename: Nicholas
authors.initials: N
authors.lastname: Moore
authors.forename: Mathieu
authors.initials: M
authors.lastname: Molimard
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000506:poisoning / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics* / Q000506:poisoning / Q000627:therapeutic use; D004347:Drug Interactions; D017809:Fatal Outcome; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000506:poisoning / Q000627:therapeutic use; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology; D010068:Oxacillin / Q000494:pharmacology* / Q000627:therapeutic use; D013207:Staphylococcal Skin Infections / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D010068:Oxacillin; D008727:Methotrexate