THE EFFECTS OF THE METHOD OF CALCULATION ON THE EVALUATION OF THE PHARMACOKINETIC PARAMETERS OF OXYTETRACYCLINE AFTER INTRAVENOUS ADMINISTRATION TO CALVES

The aim of this study was to assess the differences in the values of t he pharmacokinetic parameters attributable to the use of either linear or nonlinear regression analysis and to find the effect of weighting schemes on these differences. Six calves received 20 mg/kg oxytetracyc line i.v. Blood samples were drawn during 72 h. The assay of the drug was performed microbiologically. A bicompartmental pharmacokinetic mod el was used, kinetic analysis being carried out by linear regression ( LR) and by weighted least-squares nonlinear regression (WLSNLR). Stati stical analysis included a test for normality, the Kruskall-Wallis tes t and ANOVA with log transformation. The A(0), alpha and B-0 did not s how any statistically significant differences attributable to the math ematical method used. On the other hand, the statistically significant differences in the beta values found using the Kruskall-Wallis test a nd ANOVA with log transformation could be attributed to the different methods employed. ANOVA with log transformation determined statistical ly significant differences between the parameters obtained by linear a nalysis and those obtained by WLSNLR when the weighting (w) was 1. Whe n weights were 1/x, 1/x(2) or 1/root x, no statistically significant d ifferences were found. The optimal weighting scheme was w = 1/x(2) bec ause of a more homogeneous scatter and random distribution of residual s about the abcissa axis in a plot of weighted residuals in the ordina te versus time in the abcissa. It was concluded that the use of these different procedures can give major variations in the apparent value o f beta, the most important pharmacokinetic parameter. The correct sele ction of the weighting procedure is therefore fundamental in obtaining the best estimate of this pharmacokinetic parameter in WLSNLR.