title: A phase I clinical and pharmacological study of weekly intravenous infusions of piritrexim (BW301U).
abstract: Thirty-eight patients with advanced resistant cancers were enrolled on this study of piritrexim (PTX; BW 301U) administered intravenously weekly for 4 weeks. Of 50 courses of treatment begun, 39 evaluable 4-week courses of the drug were completed by this group of patients. Dosages ranged from 44 to 530 mg/m2/week. One patient at each dosage level received an initial weekly dose of PTX in oral form accompanied by pharmacokinetic blood sampling after the oral dose and also after a subsequent intravenous dose. Toxicities included mild nausea and vomiting, and moderate to severe peripheral vein phlebitis. Anemia and thrombocytopenia were the dominant hematological toxicities. One patient with pulmonary metastases from malignant fibrous histiocytoma experienced a 12-week partial response to PTX treatment at a dosage of 400 mg/m2/week. Pharmacokinetic analysis of plasma for PTX concentrations was accomplished utilizing a competitive protein binding assay. The estimated total body clearance ranged from 136 to 173 ml/min/1.73 m2. Mean terminal half-life after intravenous administration was 5.61 +/- 2.38 h (S.D.), and after oral administration was 5.72 +/- 2.04 h. Mean systemic bioavailability after oral administration was 75 +/- 56%.
authors.affiliation: Department of Medicine/Oncology, The University of Texas Health Science Center, San Antonio 78284.
authors.forename: G R
authors.initials: GR
authors.lastname: Weiss
authors.forename: G A
authors.initials: GA
authors.lastname: Sarosy
authors.forename: T D
authors.initials: TD
authors.lastname: Shenkenberg
authors.forename: T
authors.initials: T
authors.lastname: Williams
authors.forename: N J
authors.initials: NJ
authors.lastname: Clendeninn
authors.forename: D D
authors.initials: DD
authors.lastname: Von Hoff
authors.forename: J L
authors.initials: JL
authors.lastname: Woolley
authors.forename: S H
authors.initials: SH
authors.lastname: Liao
authors.forename: M R
authors.initials: MR
authors.lastname: Blum
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; D011743:Pyrimidines; C024530:piritrexim