The penetration of misonidazole into mature structural cartilage

Abstract

Mature cartilage may be expected to contain populations of hypoxic cells as a result of the tissues lack of direct vascularization and structure, it may therefore be at risk from possible radiosensitization. The hypoxic-cell radiosensitizing drug misonidazole Ro-07-0582 (MISO) was administered i.v. to mature New Zealand White rabbits at a dose of 100 mg/kg, and the resulting drug concentrations in both blood and ear-cartilage samples measured by HPLC. Samples were taken at regular intervals up to 4 h after administration of MISO. Blood concentrations of MISO rose rapidly to 240 microgram/ml within 5 min of administration, before falling steadily, with a t1/2 of 45 min. Cartilage levels reached a peak of 70% of the blood levels approximately 30 min after administration. The levels of MISO then fell, with a t1/2 of 44 min.