Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects.

Autor:	Blake EJ; Ferring Pharmaceuticals, Inc., Parsippany, New Jersey., Norris PM; Division of Gynecology, Department of Obstetrics and Gynecology, Miller School of Medicine, University of Miami, Miami, Florida., Dorfman SF; Ferring Pharmaceuticals, Inc., Parsippany, New Jersey. Electronic address: Sally.Dorfman@Ferring.com., Longstreth J; Longstreth & Associates, Inc., Mundelein, Illinois., Yankov VI; Ferring Pharmaceuticals, Inc., Parsippany, New Jersey.
Jazyk:	angličtina
Zdroj:	Fertility and sterility [Fertil Steril] 2010 Sep; Vol. 94 (4), pp. 1296-1301. Date of Electronic Publication: 2009 Jul 15.
DOI:	10.1016/j.fertnstert.2009.06.014
Abstrakt:	Objective: To determine pharmacokinetic profiles of two times a day and three times a day dosage regimens of Endometrin, a micronized progesterone vaginal insert for luteal support in assisted reproductive technology, compared with a gel. Design: A single-center, randomized, open-label, single-day, and multiple-day (5 days) parallel design pharmacokinetic study. Setting: University clinical research unit. Patient(s): Three groups of six healthy subjects, ages 18 to 40 years. Intervention(s): Endometrin vaginal inserts two times a day or three times a day, or gel daily. Main Outcome Measure(s): Pharmacokinetic profiles. Result(s): Progesterone serum concentrations increased rapidly following administration of Endometrin vaginal insert, producing higher peak concentrations (Cmax) and clearing faster than gel. On the single day of dosing, mean Cmax was 17.0+/-2.7 ng/mL in the two times a day group, 19.8+/-2.9 ng/mL in the three times a day group, and 6.82+/-1.69 ng/mL in the gel group. Endometrin treatments reached steady state within the first 2 days (24-36 hours), much more rapidly than the gel, which had not reached steady state by 5 days. At 5 days, the Endometrin treatments produced sustained progesterone concentrations exceeding 10 mg/mL across 24 hours. Conclusions: Endometrin vaginal inserts reached higher Cmax, produced greater systemic exposure (area under the curve 0-24), achieved steady state more rapidly, and cleared more rapidly after termination of therapy than the comparator. (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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