Ro 32-3555

The amount of hydroxyproline in non-implanted cartilage is 119.3±4.2 nM/mg and this decreases in cartilages implanted in vehicle-dosed animals to 53.6±7.1 nM/mg over a fourteen day period. Animals administered Cipemastat orally at doses of 2.5, 5, 10 and 25 mg/kg show statistically increased levels of implanted cartilage hydroxypro-line. Fourteen days after the second challenge injection of P. acnes, the area of cartilage most consistently affected by pannus is the lateral femoral condyle, which is the area analysed. In non-arthritic animals the mean cartilage area is 0.17±0.02 mm² (n=5). In arthritic animals there is a significant decrease to a mean area of 0.086±0.01 mm² (n=10). The group of animals dosed with Cipemastat (50 mg/kg, p.o.) show a significantly greater area of cartilage with a mean value of 0.126±0.012 mm² (n=9). The pannus area in vehicle-dosed animals is 0.099±0.017 mm² and in Cipemastat dosed animals 0.102±0.019 mm². Adjuvant arthritis injection of adjuvant induced two phases of swelling of the injected paw in vehicle-dosed rats. The primary swelling phase occurred between days 0 to 5 and induced an increase in paw volume of 1.9±0.1 mL; the secondary phase occurrs between day 9 to 14 and there was an increase in paw swelling of 0.98±0.08 mL. The group of animals dosed with dexamethasone (0.1 mg/kg) shows a significant reduction in both primary (0.2±0.03 mL) and secondary inflammation (0.07±0.08 mL) paw swelling as well as total inhibition of the lesion score^[1].