F. Keller(1) , D. Zellner(1) , T. Frankewitsch(1) , M.Giehl(2)
University Hospital, Medical Department, Division of Nephrology, Ulm(1)
University Hospital Benjamin Franklin, Ganzkörperzähler, Berlin(2)
In clinical practice, drug dosage adjustment is confronted with three main obstacles: first only sparse individual data is available, secondly the body of published pharmacokinetic knowledge is immens but heterogenous, and thirdly, there is only a rough estimate of the true value and the variance for a special parameter. We are on the way to build up a database with the published knowledge on pharmacokinetic parameters. A general concept of pharmacokinetics is a prerequisite for such a database, but there is no consensus and no standardization on how to represent pharmacokinetic parameters. Our proposal is based on the three closely interdependent pharmacokinetic parameters: clearance, volume and half-life. No established method is available for meta-analysis of the published values. Usually, the individual data are not recorded in the literature making NONMEM not applicable to a meta-analysis of the literature. Our preliminary analysis makes it most promising to apply different statistical methods to different sets of data. The pharmakodynamics describing the specific action of the different groups of drugs is not well defined. However, a dosage adjustment to patients with disease-related alterations of pharmacokinetics must be made by aiming at constant pharmacodynamic effects of the adjusted dosage regimens. For practical purposes we have divided the different drugs in three categories, (1) with concave, (2) linear or (3) convex pharmacodynamic relationships. Obviously, it is a fundamental mandate for the next future to initate the cross-talk between respective representatives of (a) the complex clinical demands and (b) the advanced pharmacokinetic- pharmacodynamic theory.