Standardized structure and modular design of a pharmacokinetic database.
BACKGROUND
The accumulated knowledge on drugs can be used for an individual drug dosage adjustment if it is placed at our disposal in an informatically structured form.


METHODS
We have started building 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.
Distribution and elimination. Total drug clearance and at least two parameters representing distribution and elimination processes are closely interdependent in mathematical terms (clearance = volume of distribution*rate of elimination). This relation yields the unifying concept that serves as a prerequisite for a structured recording of 30 assigned pharmacokinetic and pharmacodynamic parameters within an informatic database.
The information is retrieved and referenced from 2383 original publications by means of a standardized input module. The complete database at present contains 15,397 records for 1573 drugs. A programmed meta-analytic algorithm is used to calculate the statistical measures for the central value and variance--as available--from the pooled values of primary records. The statistically standardized parameters are extracted for 6601 pharmacokinetic parameters, and placed at the users disposal with the output module.
Following meta-analysis, 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 approach or neural networks.
Keller
F
F
University Hospital, Medical Department, Ulm, Germany. fieder.keller@medizin.uni-ulm.de
Frankewitsch
T
T
Zellner
D
D
Simon
S
S
Czock
D
D
Giehl
M
M
D000465:Algorithms; D001499:Bayes Theorem; D016208:Databases, Factual; D004346:Drug Information Services; D006801:Humans; D007668:Kidney / Q000502:physiology; D016571:Neural Networks, Computer; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010599:Pharmacokinetics; D051437:Renal Insufficiency / Q000503:physiopathology; D015203:Reproducibility of Results
D004364:Pharmaceutical Preparations