The pharmacokinetics in mice and dogs of nitroimidazole radiosensitizers and chemosensitizers more lipophilic than misonidazole

Abstract

We have examined the pharmacokinetic properties of nitroimidazole radiosensitizers and chemosensitizers more lipophilic than misonidazole (MISO). In dogs, 2 analogues showed comparable peak plasma concentrations with considerably shorter half-lives (t1/2) and reduced areas under curves (AUC). Benznidazole (Ro 07-1051) had a much longer t1/2, a higher AUC, and somewhat higher peak concentrations. In mice tumor/plasma, brain/plasma, and tumor/brain ratios were generally similar to MISO, as was penetration of brain and peripheral nerve by benznidazole in dogs. Selection of lipophilic analogues with appropriate pharmacokinetic properties may facilitate accommodation of the potentially different requirements for improved radiosensitization or chemosensitization.