Pharmacokinetic Profile and Endocrine Effects of Posatirelin Treatment in Healthy Elderly Subjects
| Autor: | Gianpaolo Reboldi, Umberto Senin, Fausto Santeusanio, Antonio Cherubini, R. Girardello, David T. Lowenthal, Barbara Palumbo, L. Ambrosoli, Lucilla Parnetti, A. Poli |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Thyroid Hormones medicine.medical_specialty Hydrocortisone Metabolic Clearance Rate Basal (phylogenetics) Pharmacokinetics Internal medicine Humans Medicine Endocrine system Pharmacology (medical) Circadian rhythm Thyrotropin-Releasing Hormone Aged Aged 80 and over Pharmacology business.industry Prolactin Circadian Rhythm posatirelin aging brain Endocrinology Area Under Curve Female business Intramuscular injection Central Nervous System Agents medicine.drug Hormone |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0091-2700 |
| DOI: | 10.1002/j.1552-4604.1996.tb04256.x |
| Popis: | The pharmacokinetics and endocrine effects of a therapeutic dose (10 mg/day) of posatirelin (L-pyro-2-aminoadipyl-L-leucyl-L-prolinamide) were investigated in healthy elderly subjects. Posatirelin was given once daily by intramuscular injection for 7 days. Pharmacokinetic parameters were estimated using a model-independent approach. The plasma concentrations of free triiodotyronine (FT 3 ), free thyroxine (FT 4 ), and thyroid-stimulating hormone (TSH) and the circadian rhythms of prolactin and cortisol were considered as indicator variables of endocrine response to posatirelin administration. Posatirelin was well tolerated and no significant adverse effects were observed during the study. Peak plasma concentration (C max ), time of peak plasma concentration (t max ), area under the plasma concentration-time curve from time zero to infinity (AUC 0- ∞), elimination half-life (t 1/2 ), and total clearance (Cl/F) were measured after single-dose intramuscular injection (day 1) and after multiple-dose administration (day 7). There were no significant changes in these parameters after multiple-dose administration (day 7). Posatirelin induced a progressive reduction in basal TSH levels and maximum response. There were no significant changes during treatment in the time at which basal levels of FT 3 and FT 4 occurred, and these levels remained within the normal range throughout the study. The circadian rhythms of cortisol and prolactin were not influenced by posatirelin treatment. The pharmacokinetics of posatirelin were not time dependent, and the drug did not accumulate after multiple-dose administration. Short-term treatment with posatirelin did not induce clinically relevant endocrine consequences in healthy elderly subjects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text