Dose-response studies of gentamicin nephrotoxicity in rats with experimental renal dysfunction. I. Subtotal surgical nephrectomy.

Gentamicin pharmacokinetics and nephrotoxicity have not been widely studied in animals with preexisting renal dysfunction, despite the fact that nephrotoxicity is a continuing manifestation of clinical therapy. The present study contrasted the dose-response nephrotoxicity of gentamicin in control rats with that of rats with renal insufficiency secondary to subtotal (2/3) surgical nephrectomy. Total daily doses ranging from 0 to 120 mg/kg were given in a divided regimen, every 8 hr and doses were reduced by doubling the interval in subtotally nephrectomized (Nx) rats, in proportion to impaired renal elimination on the first day of gentamicin administration.

Pharmacokinetics and comparative nephrotoxicity of fixed-dose versus fixed-interval reduction of gentamicin dosage in subtotal nephrectomized dogs.

There is presently no consensus as to the relative safety of fixed-interval/reduced dose (FI) vs fixed-dose/increased interval (FD) dosage adjustment regimens for use in renal insufficiency. This study compared their nephrotoxic potential using gentamicin in beagle dogs with renal insufficiency secondary to subtotal surgical nephrectomy. Pharmacokinetic analysis in six dogs showed that this surgical procedure resulted in a decreased total body clearance of drug and a marginally contracted volume of the central compartment.

Application of biplot methods to the multivariate analysis of toxicological and pharmacokinetic data.

The biplot technique was applied to aminoglycoside renal toxicological and pharmacokinetic data in beagles. The biplot obtains a two-dimensional approximation to a matrix and plots row effects and column effects jointly, depicting relationships among different observed variables and simultaneously showing the relationship of experimental units as individuals and as treatment groups to those variables. This graphical representation of the matrix allows inspection of relationships, trends, clusters, approximate correlations, and variances existing in the data.