An Updated Comparison of Drug Dosing Methods

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Abstract
The resurgence of the use of and interest in vancomycin, in conjunction with the high degree of interpatient variability in its pharmacokinetic profile, has prompted the development of many and varied dosing methods. Several dosing nomograms have been proposed and evaluated, methods which are useful for initial dosing but do not allow for individualisation of dosage. Given these constraints, several investigators have attempted to apply conventional least-squares regression techniques and, more recently, Bayesian methodologies using either 1- or 2-compartment pharmacokinetic models. Comparative information evaluating algorithmic methods demonstrates that those of Moellering and Lake offer the least biased and most precise predictions of vancomycin dosage. Patient individualisation using conventional least-squares methodology offers some improvement over nomogram-based methods, both in predictive performance and in dosage adjustment once serum concentration data are available. Overall, the latest data indicate that regimens which incorporate Bayesian principles tend to give better results than nomogram-based or conventional least-squares dosing methods for this drug. Despite the advances in methods for dosing vancomycin, several questions remain to be answered. A lack of convincing evidence of a correlation between serum concentrations and therapeutic outcome has prompted debate over the need for serum concentration monitoring and, if it is needed, over which patient population would most benefit. Secondly, little comparative information is currently available as to the dosing of vancomycin in paediatric and neonatal patient populations. Several nomograms for initial dosing have been proposed, but only 2 have been subject to subsequent testing. Finally, information regarding cost-effectiveness and the quality of patient outcome is lacking from the current literature.