Description of the time course of the prolactin suppressant effect of the dopamine agonist CQP201-403 by an integrated pharmacokinetic-pharmacodynamic model

Details

Serval ID
serval:BIB_AC017405F649
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Description of the time course of the prolactin suppressant effect of the dopamine agonist CQP201-403 by an integrated pharmacokinetic-pharmacodynamic model
Journal
British Journal of Clinical Pharmacology
Author(s)
Grevel  J., Brownell  J., Steimer  J. L., Gaillard  R. C., Rosenthaler  J.
ISSN
0306-5251 (Print)
Publication state
Published
Issued date
07/1986
Volume
22
Number
1
Pages
1-13
Notes
Clinical Trial
Comparative Study
Journal Article
Randomized Controlled Trial --- Old month value: Jul
Abstract
Six male volunteers (mean age 24 years) received a single oral dose of 0.025 mg CQP201-403 and placebo in a randomised double-blind crossover design. Fifteen plasma samples were collected over 48 h and were assayed by radioimmunoassay for drug substance and prolactin (PRL). Three of the samples were drawn during sleep on the first study day. The pharmacological effect (E%) of CQP201-403 was expressed as reduction in plasma PRL levels. The pharmacokinetic (PK)-pharmacodynamic (PD) model consisted of two kinetic compartments and an effect compartment linked to the central compartment. A sigmoid Emax model (Hill equation) described the relationship between the drug concentration in the effect compartment and E%. Curve-fitting of PK and PD data provided individual parameter estimates which served to generate computer-simulated PK and PD profiles after single and multiple doses in order to: investigate the in vivo concentration-effect relationship; evaluate the consequence of dosage reduction on the steady-state PD profile; and study the robustness of the response to changes in drug potency and bioavailability.
Keywords
Adult Dose-Response Relationship, Drug Double-Blind Method Ergolines/blood/*pharmacology Humans Kinetics Male *Models, Biological Prolactin/*blood Radioimmunoassay Random Allocation Software Time Factors
Pubmed
Web of science
Create date
15/02/2008 16:57
Last modification date
20/08/2019 15:16
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