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. Biplots were generated from gentamicin dosage regimen nephrotoxicity data. Six dogs classified as being intoxicated by established indicators of renal toxicity were a distinct cluster. A cluster of nonintoxicated dogs was separated into two groups approximating nephrectomized and normal dogs, thus revealing variables significant in separating toxic and nontoxic as well as nephrectomized and normal dogs. Biplots from pharmacokinetic data were able to separate different renal disease states on the basis of disease-induced changes in gentamicin pharmacokinetic parameters. In conclusion, the biplot technique proved to be a very useful tool in exploring this type of data by revealing clear relationships between nephrotoxicity and physiological and pharmacokinetic variables and by separating different disease states based on these data.