title: Relationship between the pharmacokinetics and toxicity of mitozolomide.
abstract: The cytotoxic drug mitozolomide has been found to cause unpredictably severe thrombocytopenia during phase I and II clinical trials. In an attempt to relate dose and pharmacokinetic parameters to toxicity, we measured plasma concentrations of mitozolomide in 14 patients with a range of malignancies. There were significant correlations (Spearman rank correlation test) between drug clearance and AUC and white blood cell nadir. The pharmacokinetic and toxicity data were not normally distributed; therefore, it was not possible to construct predictive nomograms for toxicity based on linear regression analysis.
authors.affiliation: CRC Department of Medical Oncology, University of Glasgow, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: J A
authors.initials: JA
authors.lastname: Slack
authors.forename: P
authors.initials: P
authors.lastname: Secrett
authors.forename: M F
authors.initials: MF
authors.lastname: Stevens
authors.forename: G R
authors.initials: GR
authors.lastname: Blackledge
authors.forename: C
authors.initials: C
authors.lastname: Bradley
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009588:Nitrogen Mustard Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D010976:Platelet Count
chemical_list: D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C040369:mitozolomide