Pharmacokinetic Studies on Some Novel (2-Nitro-1-Imidazolyl) Propanolamine Radiosensitizers

Abstract

One area of current interest in radiosensitizer development is in the use of nitroimidazoles of a more polar nature than misonida-zole, combining the benefits of a shorter half-life, and thus reduced tissue exposure, which has been correlated with the neuropathy observed with misonidazole (1), while also minimising brain penetration through the blood-brain barrier (2). In the Gray Laboratory development programme, one aim has been to attempt to combine the advantages of a highly polar compound with an increased radiosensi-tizing efficiency by including basic functions in the 2-nitroimida-zole side chain. Preliminary data for one of these, the propanol-amine Ro 03–8799, indicating favourable pharmacokinetic properties following intraperitoneal administration have already been published (3).