Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs

Pharmacokinetic disposition of gentamicin was studied in 69 dogs--12 control and 33 subtotally nephrectomized dogs representing combined data from previous experimental studies, and 24 dogs with a variety of diseases and degrees of renal dysfunction. Drug disposition varied considerably within and between diseases, and dosages had to be altered to achieve therapeutic drug concentrations and to minimize drug toxicosis. Decreased drug clearance when serum creatinine and urea nitrogen concentrations are normal may be indicative of subclinical renal disease and therefore may indicate a predisposition for development of nephrotoxicosis. Results of the study indicated the need to individualize aminoglycoside dosage regimens on the basis of pharmacokinetic disposition of drug, especially in dogs with preexisting subclinical renal dysfunction. Because of the large variability normally encountered in dogs with various diseases, monitoring of renal function alone is not sufficient to accurately predict gentamicin clearance, volume of distribution, or half-life.