Evaluation of enzymuria as an indicator of amikacin-induced renal damage in guinea pigs.
Guinea pigs were injected subcutaneously for 10 days with amikacin (AK) at a dose of 0, 100, 200 or 400 mg/kg body wt. per day. The total daily dose was administered in either a single injection or divided equally and given as two daily injections. After the 10 days of AK treatment, uptake of the organic cation, tetraethylammonium (TEA) into renal cortical slices was inhibited in a dose-related manner. Changes in renal tubular morphology also increased with higher doses. The urinary excretion of the enzymes, N-acetyl-beta-D-glucosaminidase (NAG), and alkaline phosphatase (ALP) significantly increased during the course of AK treatment, however, due to the large intragroup variability, the daily fluctuations and the absence of any distinct trends in urinary enzyme excretion it was difficult to establish a dose-relationship between AK-induced renal damage and the resultant enzymuria. At doses of 100 and 200 mg/kg body wt., the two-injection regimen resulted in the greater renal accumulation of AK and damage as reflected by a greater inhibition of TEA uptake and greater changes in renal tubular morphology. In contrast, this difference in toxicity could not be detected with enzymuria again due to the large intragroup variability and the absence of discernable excretion patterns of NAG and ALP. Thus, neither NAG nor ALP appear to be suitable quantitative markers of AK-induced nephrotoxicity.
Suzuki
C A
CA
Drug Toxicology Division, Sir F.G. Banting Research Centre, Ottawa, Ontario, Canada.
Thomas
B H
BH
Mueller
R
R
D000118:Acetylglucosaminidase / Q000652:urine*; D000469:Alkaline Phosphatase / Q000652:urine*; D000583:Amikacin / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D000644:Quaternary Ammonium Compounds / Q000493:pharmacokinetics; D013997:Time Factors
D000644:Quaternary Ammonium Compounds; C066585:triethylammonium cation; D000583:Amikacin; D003404:Creatinine; D000469:Alkaline Phosphatase; D000118:Acetylglucosaminidase