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.
Highlights
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
FIGuRE.-Mean misonidazole concentrations ( s.e.) in rabbit blood (-a-) and cartilage -- ) after administration of 100 mg/kg i.v. misonidazole exponential curve fitted to the data by the method of weighted least squares gives a t1/2 of 45 0 min + 0-36 (s.e.) in blood at this dose
The MISO concentrations found in both the blood and cartilage samples are shown in the Figure
Summary
Summary.-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 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. THE INVESTIGATION of hypoxic-cell sensitizers for use in the radiotherapy of tumours must include an examination of normal tissues which would be expected to contain hypoxic cells One such tissue is mature structural cartilage. Silver (1975) has found that the oxygen tension in the centre of blocks of articular cartilage growing in rabbit-ear chambers is 07-1.0 kPa. Rabbit-ear cartilage has been used to determine whether misonidazole (Ro-07-0582 MISO) reaches the tissue and achieves a sufficiently high concentration to cause sensitization during subsequent irradiation
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