Selection of doses for phase II clinical trials based on pharmacokinetic variability consideration.
J Clin Pharmacol
; 37(8): 673-8, 1997 Aug.
Article
em En
| MEDLINE
| ID: mdl-9378839
ABSTRACT
Pharmacokinetic variability is an important component of the total variability in drug response, but Phase II dose-response trials frequently are designed without considering this important factor. Mixed-effects model simulation was performed to examine overlap of patient area under the concentration-time curve (AUC) values between doses for drugs with differing inter- and intrapatient pharmacokinetic variability. Based on the results of this simulation, a dose increment of at least threefold is needed to ensure that drug exposure does not overlap in at least 50% of the patient population for a drug that exhibits greater than 25% variability. In contrast, an increment factor of 2 is normally sufficient to produce the same degree of resolution when the variability is less than 25%. These results suggest that a more aggressive choice of administration increments could lead to a better separation in systemic drug exposure between doses. This needs to be balanced against the therapeutic window of an individual drug product.
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Base de dados:
MEDLINE
Assunto principal:
Farmacocinética
/
Preparações Farmacêuticas
/
Ensaios Clínicos Fase II como Assunto
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
1997
Tipo de documento:
Article