Single- and multiple dose pharmacokinetics of lonidamine in patients suffering from non-small-cell lung cancer

Pharmacokinetic studies of lonidamine (1-[2,4-dichlorobenzyl]- 1H- indazole- 3-carboxylic acid, Doridamina: CAS 50264-69-2) in humans showed a wide variation of the plasma concentration-time profiles following a single peroral dose of 300 mg (Cmax between 6.5 and 40.9 micrograms/ml, tmax between 0.75 and 5.5 h). In order to investigate single and multiple dose pharmacokinetics after peroral administration of this chemotherapeutic compound, a study was performed involving 12 patients with non-small-cell malignancies of the lungs. Plasma and urinary concentration profiles were analyzed for determination of the pharmacokinetic parameters for lonidamine after single dose administration and in the steady state. In addition, age dependency and the presence of liver induction or inhibition was evaluated. Results indicate that steady state was reached after 2 dosing intervals of 12 h and no changes in liver metabolism or age dependent pharmacokinetics could be revealed after 4 days of multiple dose treatment.