ISSN:
1432-0738
Keywords:
Ofloxacin
;
Quinolones
;
Marmosets
;
Rats
;
Arthropathia
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Arthropathia in juvenile animals is the most important toxic effect induced by quinolones. We conducted pharmacokinetic and morphological studies with ofloxacin on non-human primates (Callithrix jacchus, Marmosets) and rats. In the marmoset, electron microscopy and the application of immuno-morphological methods proved to be suitable for the detection of specific alterations in cartilage (e. g. loss of proteoglycanes and altered chondrocytes). Subsequently performed electron microscopic examinations in rats showed similar specific alterations of the femur cartilage surface after multiple oral applications of 600 mg ofloxacin/kg body wt. These results were correlated with pharmacokinetic data obtained for the same species. After single oral application of 100, 300 or 600 mg ofloxacin/kg body wt to 5 week-old rats peak plasma levels were achieved 15–45 min after administration indicating a rapid absorption of the drug. The following peak concentrations were measured for the three doses applied (mean±SD): 8.9±2.1, 22.6±7.5 mg/l and 33.5±9.8 mg/l, respectively. After 360 min the concentrations were 1.1±0.4, 5.9±2.5 and 15.9±5.1 mg/l, respectively. After subcutaneous injection of 100 mg ofloxacin/kg body wt the mean peak concentration was 27.7±2.6 mg/l after 45 min (0.5±0.2 mg/l after 360 min). In the marmoset higher plasma concentrations were measured with comparable doses. One, 3, and 6 h after the last of nine administrations of 200 mg ofloxacin/kg body wt, the mean (±SD) plasma concentrations were: 42.7±16.7, 40.6±9.5, and 26.5±3.6 mg ofloxacin/l plasma. Typical alterations of the joint cartilage of juvenile rats (e. g. opened chondrocyte cavities, swelling of rough endoplasmic reticulum and mitochondrial swelling in the chondrocytes) were induced by oral administration of ofloxacin at doses that were approximately 100 times higher than therapeutic ones, but led to peak plasma concentrations which were only approximately 10 times above the therapeutic level. Since we found corresponding cartilage alterations in marmosets and rats, this species provides a convenient model for additional studies on chondrotoxic effects of quinolones.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02010725
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