Abstract

The plasma levels of lonidamine have been studied in 24 breast or lung cancer patients as part of the Phase II evaluation of the drug. The pharmacokinetic studies were performed when the patients had been on oral lonidamine therapy for 27 to 47 days (mean 32 days) and the studies were conducted over a 24 hour period. Lonidamine was administered in three divided doses of 150 mg (t = 0h), 150 mg (t = 7h), and 150 mg or 300 mg (t = 14h). Plasma levels of lonidamine were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. Lonidamine was detected in the plasma of all patients studied, and the absolute range for the peak plasma levels of the drug following the first and second doses were 4.6-33.8 and 4.8-33.3 micrograms/ml, respectively. The range of times after administration at which the peak occurred was 0.5 to 4.2 hours for the first dose and 0.5 to 4.1 hours for the second. The absolute range for the trough levels observed over the 24-hour study period was 1.0 to 12.6 micrograms/ml and in 19 of the patients it was possible to define the apparent half life of lonidamine that was found to be within the range 2.5 to 11.7 hours. In addition to lonidamine, a number of fluorescent components were detected in the plasma of patients following lonidamine treatment that were not detected in pretreatment plasma samples. One component, a compound that eluted from the HPLC more rapidly than lonidamine, was found in some patients to be sensitive to hydrolysis with beta-glucuronidase. Comparison of the pharmacokinetic data with patient characteristics and clinical biochemistry results failed to establish any clear relationship. Similarly there was no relationship between lonidamine pharmacokinetics and either drug-induced myalgia or testicular pain. Insufficient responses were seen in the patient group studied to allow the relationship between lonidamine pharmacokinetics and response to be evaluated.