Dose-response curves for predicting misonidazole-induced peripheral neuropathy.
Using pharmacokinetics determined for 27 patients who received iv misonidazole, we have studied the relationship between various pharmacokinetic parameters and the probability of observing peripheral neuropathy. By plotting the probability of observing peripheral neuropathy as a function of each individual parameter and using a linear logistic regression model, we have 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 well prove useful for other toxic agents used in cancer treatment.
D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000188:drug therapy; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008920:Misonidazole / Q000009:adverse effects* / Q000378:metabolism; D009593:Nitroimidazoles / Q000009:adverse effects*; D012516:Osteosarcoma / Q000188:drug therapy; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D011336:Probability
D009593:Nitroimidazoles; D008920:Misonidazole