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.
Kerr
D J
DJ
CRC Department of Medical Oncology, University of Glasgow, U.K.
Slack
J A
JA
Secrett
P
P
Stevens
M F
MF
Blackledge
G R
GR
Bradley
C
C
Kaye
S B
SB
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
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; C040369:mitozolomide