Effect of diabetes on disposition and renal handling of cefazolin in rats.
The effects of early-stage diabetes on disposition and renal handling of cefazolin (CEZ) were investigated in streptozotocin-induced diabetic rats. Significant increase in renal clearance was found in the diabetic rats (88%) and a strong correlation was obtained between renal and systemic clearance; however, there was no change in the volume of distribution. The results suggest that systemic clearance was increased as the result of enhancement of urinary excretion rate. Unbound fraction of CEZ in plasma was also increased by 60% in the diabetic rats and the increase may be due to the increase in glycosylated protein and plasma-free fatty acids. The filtration clearance for free drug in diabetic rats, which was estimated as glomerular filtration rate, was increased by about 1.9-fold compared to the normal rats, but the secretion clearance did not change in the two groups. Since kidney hypertrophy was observed in the diabetic rats, filtration and secretion clearance for free drug were normalized by means of kidney weight. After normalization for kidney weight, the two parameters were significantly reduced, indicating that the true kidney functions were impaired under the diabetic state. The parameters for CEZ secretion, maximum velocity and Michaelis-Menten constant, were also reduced in diabetic rats, suggesting that proximal tubule cell functions for secretion were altered in the diabetic rats. These results suggest that systemic and renal clearance was apparently increased in early-stage diabetes, whereas true kidney functions were impaired.
Nadai
M
M
Department of Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Yoshizumi
H
H
Kuzuya
T
T
Hasegawa
T
T
Johno
I
I
Kitazawa
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002437:Cefazolin / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D005230:Fatty Acids, Nonesterified; D002437:Cefazolin