[Pharmacokinetic-pharmacodynamic modeling in phase II of drug development. A comparative study with young and old volunteers with benzdiazepine as an example].
Especially for medical disciplines like anesthesiology, which represent only a small economic market, drug development is a cost intensive and with respect to financial aspects a high risk task. This situation requires methods, which in the early stages of the drug development process of an interesting compound allow the establishment of a reliable and valid data set, in order to make decisions on the continuation or discontinuation of a project. Given a compound out of the group of benzodiazepines as an example this paper represents todays methods of integrated pharmacokinetic-pharmacodynamic modelling as well as the special computer aided strategies of drug dosing as powerful tools in the anaesthetic drug development process. It is shown that one can generate data concerning differences in drug requirement and drug duration in the therapeutic dose range between different groups of possible patients, e.g. young and elderly, as early as the early phase II. It is concluded that these clinical pharmacological tools and the high resolution data generated by them facilitate the Go/No-Go decision to proceed to phase III and enhance the likelihood of passing phase III successfully.
Albrecht
S
S
Klinik für Anästhesiologie, Universität Erlangen, Nürnberg.
Hering
W
W
Ihmsen
H
H
Schwilden
H
H
Schüttler
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000465:Algorithms; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D001569:Benzodiazepines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics / Q000494:pharmacology; D008954:Models, Biological; D010080:Oxazoles / Q000493:pharmacokinetics / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010080:Oxazoles; C110142:Ro 48-8684; D001569:Benzodiazepines; D008874:Midazolam