Relationship between the pharmacokinetics and toxicity of mitozolomide
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.
KeywordsPlasma Concentration Thrombocytopenia White Blood Cell Linear Regression Analysis Rank Correlation
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