A minimax approach to the single-point method of drug dosing

The single-point dose prediction method is based on the observation that for drugs obeying single compartment elimination kinetics there is a nearly constant reciprocal relation between the plasma level at a fixed time following a single loading dose and the dose that is required to maintain the desired steady state plasma level of the drug. This paper describes an improved method for choosing a plasma sampling time and a proportionality constant. It applies to either drugs administered intravenously or to drugs whose rates of absorption from the site of administration are very rapid compared to their rates of elimination from the body. The sampling time and proportionality constant chosen are those that minimize the maximum relative deviation of the maintenance dose estimated by the single-point method from the dose that would be estimated if the individual's true elimination rate constant were known. The paper also supplies a method to determine the maximum error that may be introduced into the estimation of the maintenance dose by using the single-point method.This investigation was supported in part by NIH National Research Service Award GM 09279-02 (M.M.B.), NIH grant R01 AM 25744-07, and NATO Collaborative Research Grant 85/0207 (E.M.L.). M.M.B. is a Daland Scholar of the American Philosophical Society.