Comparison of cephaloridine renal accumulation and urinary excretion between normoglycemic and diabetic animals.
The renal toxicity of cephaloridine is reduced in a streptozotocin diabetic rat model. This study tested the hypothesis that renal cortical cephaloridine accumulation was diminished in diabetic rats. The following studies also investigated whether renal excretion was enhanced in diabetic rats. Male Fischer 344 rats were randomly divided into normoglycemic or diabetic groups. Diabetes was induced by injection (intraperitoneal, i.p.) of 35 mg/kg streptozotocin. Normoglycemic and diabetic rats were injected (i.p.) with 1500 mg/kg cephaloridine. Peak plasma cephaloridine levels were similar in both groups. Renal cortical accumulation was diminished (P < 0.05) in the diabetic group 1 and 4 h after cephaloridine injection. Urinary cephaloridine excretion was enhanced (P < 0.05) in the diabetic group relative to the normoglycemic animals during the first 4 h after cephaloridine injection. Comparisons between normoglycemic and diabetic groups indicated renal cortical cephaloridine accumulation was lower in the diabetic group. These findings would support the hypothesis that reduced cephaloridine toxicity in diabetic animals was due to reduced renal cortical accumulation of the toxin. These data also demonstrate that cephaloridine excretion was enhanced in the diabetic group and may contribute to the diminished renal accumulation.
Valentovic
M A
MA
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25704-9388, USA.
Ball
J G
JG
Rogers
B A
BA
D000818:Animals; D002509:Cephaloridine / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D002511:Cephalosporins / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344
D002511:Cephalosporins; D002509:Cephaloridine