QUINOLONE-INDUCED ARTHROPATHY - EXPOSURE OF MAGNESIUM-DEFICIENT AGED RATS OR IMMATURE RATS, MINERAL CONCENTRATIONS IN TARGET TISSUES AND PHARMACOKINETICS
C. Forster et al., QUINOLONE-INDUCED ARTHROPATHY - EXPOSURE OF MAGNESIUM-DEFICIENT AGED RATS OR IMMATURE RATS, MINERAL CONCENTRATIONS IN TARGET TISSUES AND PHARMACOKINETICS, Archives of toxicology, 72(1), 1997, pp. 26-32
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.