DOSE-RESPONSE CURVES FOR PREDICTING MISONIDAZOLE-INDUCED PERIPHERAL NEUROPATHY

  • 1 January 1982
    • journal article
    • research article
    • Vol. 66  (9) , 1743-1750
Abstract
Using pharmacokinetics determined for 27 patients who received i.v. misonidazole [a hypoxic cell radiosensitizer], the relationship between various pharmacokinetic parameters and the probability of observing peripheral neuropathy was studied. By plotting the probability of observing peripheral neuropathy as a function of each individual parameter and using a linear logistic regression model, the following results were found: a general sigmoid response relating the observations of peripheral neuropathy to the area under the pharmacokinetic curve (AUC); the total cumulative dose throughout the course; the plasma concentration; the plasma elimination half-life, and the total cumulative AUC. By using linear logistic regression analysis, the best correlation with observing peripheral neuropathy was seen with the AUC. Statistical considerations are discussed in depth. This type of analysis may prove useful for other toxic agents used in cancer treatment.

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