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An agonist-antagonist interaction model for prolactin release following risperidone and paliperidone treatment.
- Source :
-
Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 2009 Apr; Vol. 85 (4), pp. 409-17. Date of Electronic Publication: 2008 Dec 24. - Publication Year :
- 2009
-
Abstract
- A mechanistic pharmacokinetic/pharmacodynamic model is presented, characterizing the time course of prolactin in healthy as well as schizophrenic subjects following the administration of various doses and formulations of the antipsychotic drugs risperidone and paliperidone. Prolactin concentrations from nine studies (1,462 subjects) were analyzed in NONMEM. A competitive agonist-antagonist interaction model described the competition between these drugs and dopamine for the D(2) receptors that regulate prolactin release. Tolerance development was explained by a feedback loop with prolactin stimulating dopamine release, whereas models wherein tolerance is described in terms of depletion of a prolactin pool did not explain the data well. The diurnal prolactin rhythm was described by a two-period cosine function. Baseline prolactin was health-status dependent and higher in women than in men, although the drug-induced release was less than proportional to baseline. This quantitative mechanism-based model is the first to describe prolactin release in patients, and it confirms that paliperidone and risperidone have similar potencies for prolactin release.
- Subjects :
- Drug Interactions physiology
Female
Humans
Isoxazoles pharmacology
Male
Paliperidone Palmitate
Prolactin agonists
Prolactin antagonists & inhibitors
Pyrimidines pharmacology
Risperidone pharmacology
Isoxazoles blood
Models, Biological
Prolactin blood
Prolactin metabolism
Pyrimidines blood
Risperidone blood
Subjects
Details
- Language :
- English
- ISSN :
- 1532-6535
- Volume :
- 85
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Clinical pharmacology and therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 19109590
- Full Text :
- https://doi.org/10.1038/clpt.2008.234