QUINOLONE-INDUCED ARTHROPATHY - EXPOSURE OF MAGNESIUM-DEFICIENT AGED RATS OR IMMATURE RATS, MINERAL CONCENTRATIONS IN TARGET TISSUES AND PHARMACOKINETICS

Quinolone treatment or magnesium deficiency induce identical cartilage lesions in juvenile rats and show additive arthropathogenic effects. It has been shown previously that neither condition is arthropathogeni c in 8-week-old rats. Joint cartilage from aged individuals is rather prone to pathological alterations but information on prolonged quinolo ne treatment and/or dietarily induced magnesium deficiency in aged ani mals is not available. We treated magnesium-deficient (n = 9) aged Wis tar rats (age 15 months) and age-matched controls with daily doses of 600 mg of loxacin/kg body wt. by gastric intubation for 28 days. Furth er groups of magnesium-deficient and control rats (n = 9 and n = 10, r espectively) received the vehicle only. Peak plasma concentrations of ofloxacin in adult rats were 20.5 +/- 5.6 mg/l (mean +/- SD) following treatment with a single dose of 600 mg/kg body wt. At the end of the experiment the degree of magnesium deficiency was most pronounced in p lasma (Mg2+-def., 0.33 +/- 0.12 mmol/l; control. 0.97 +/- 0.08 mmol/l) and less pronounced in sternal cartilage (Mg2+-def., 10.8 +/- 3.6 mmo l/kg dry wt; control, 13.3 +/- 2.5 mmol/kg dry wt), whereas the magnes ium concentration in femoral bone remained unchanged (Mg2+-def., 201 /- 13 mmol/kg dry wt; control, 204 +/- 11 mmol/kg dry wt). Histologica l investigation of the knee joints revealed no cartilage lesions follo wing ofloxacin treatment, magnesium deficiency or a combination of bot h conditions. By contrast, cartilage lesions such as scars and erosion s of the joint surface, chondrocyte clusters within acellular areas of the cartilage matrix and persisting clefts were detectable in knee jo ints from 7 of 10 adult rats (age 9 months) which had been treated wit h 4 x 600 mg fleroxncin/kg body wt. at 5 weeks of age. Mean plasma con centration of fleroxacin in juvenile rats was approx, 50 mg/l between 1.5 and 6 h after dosing and the drug was still detectable in plasma 4 8 h after dosing (0.4 +/- 0.1 mg/l). Our data indicate that joint cart ilage in aged rats is not altered by a 4-week quinolone treatment, eve n during magnesium deficiency. Cartilage lesions in adult rats were on ly detectable if the animals had been treated during the sensitive pha se at 5 weeks postnatally.