STANDARDIZED STRUCTURE AND MODULAR DESIGN OF A PHARMACOKINETIC DATABASE

Background: the accumulated knowledge on drugs can be used for an indi vidual drug dosage adjustment if it is placed at our disposal in an in formatically structured form. Theory and methods: we have started buil ding up a pharmacokinetic database aimed at adjusting drug dosages, in exemplary form, to patients with renal impairment. Parameters needed for the three dosage adjustment rules (Dettli, Kunin, Holford) and the most general concept of pharmacokinetics constituted the theoretical basis. Two processes pertain to all drugs: distribution and eliminatio n. Total drug clearance and at least two parameters representing distr ibution and elimination processes are closely interdependent in mathem atical terms (clearance = volume of distributionrate of elimination). This relation yields the unifying concept that serves as a prerequisi te for a structured recording of 30 assigned pharmacokinetic and pharm acodynamic parameters within an informatic database. Solutions and res ults: the information is retrieved and referenced from 2383 original p ublications by means of a standardized input module. The complete data base at present contains 15397 records for 1573 drugs. A programmed me ta-analytic algorithm is used to calculate the statistical measures fo r the central value and variance-as available-from the pooled values o f primary records. The statistically standardized parameters are extra cted for 6601 pharmacokinetic parameters, and placed at the users disp osal with the output module. Practical utility: following meta-analysi s, published pharmacokinetics can be used as statistical estimates of population parameters. The statistical estimates with variances permit an individual drug dosage adjustment by applying the Bayesian approac h or neural networks. (C) 1998 Elsevier Science Ireland Ltd. All right s reserved.