PROSPECTIVE EVALUATION OF A MODEL FOR THE PREDICTION OF MILK - PLASMA DRUG CONCENTRATIONS FROM PHYSICOCHEMICAL CHARACTERISTICS

1 Milk:plasma (M/P) drug concentration ratios predicted by a model utilizing pKa, plasma protein binding and octanol:water partition coefficients have been compared with actual M/P values for 10 basic drugs. 2 There was a close relationship between predicted and observed M/P ratios with a coefficient of determination r2 of 0.97. However, there was a proportional error. 3 The data were transformed by taking logs of predicted and observed (M/P + 1) values. Regression analysis resulted in an r2 of 0.95, an intercept on the Y-axis not significantly different from zero and a slope not significantly different from one. 4 The 95% confidence interval around a single prediction revealed an error between 150% for the lowest and 23% for the highest M/P ratios. The error is therefore lowest for the drugs likely to have the greatest transfer into milk. 5 There was no significant bias in the predictions. 6 The model was refined by multiple linear regression analysis utilising the observed M/P ratios for the 10 basic drugs in addition to those of the original drugs. The revised equation resulted in an improvement in the explained variance. 7 Protein binding was the most important single predictor. 8 The results confirm that M/P ratios for basic drugs can be predicted accurately from their physicochemical characteristics.