Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1296-1301 |
| Number of pages | 6 |
| Journal | Fertility and Sterility |
| Volume | 94 |
| Issue number | 4 |
| DOIs | |
| State | Published - Sep 1 2010 |
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Keywords
- assisted reproductive technology
- Endometrin
- in vitro fertilization
- IVF
- luteal support
- pharmacokinetics
- PK
- progesterone
- progesterone supplementation
- vaginal
ASJC Scopus subject areas
- Obstetrics and Gynecology
- Reproductive Medicine
Cite this
Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects. / Blake, Emily J.; Norris, Paul M.; Dorfman, Sally Faith; Longstreth, James; Yankov, Vladimir I.
In: Fertility and Sterility, Vol. 94, No. 4, 01.09.2010, p. 1296-1301.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Single and multidose pharmacokinetic study of a vaginal micronized progesterone insert (Endometrin) compared with vaginal gel in healthy reproductive-aged female subjects
AU - Blake, Emily J.
AU - Norris, Paul M.
AU - Dorfman, Sally Faith
AU - Longstreth, James
AU - Yankov, Vladimir I.
PY - 2010/9/1
Y1 - 2010/9/1
N2 - 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.
AB - 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.
KW - assisted reproductive technology
KW - Endometrin
KW - in vitro fertilization
KW - IVF
KW - luteal support
KW - pharmacokinetics
KW - PK
KW - progesterone
KW - progesterone supplementation
KW - vaginal
UR - http://www.scopus.com/inward/record.url?scp=77956188164&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77956188164&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2009.06.014
DO - 10.1016/j.fertnstert.2009.06.014
M3 - Article
C2 - 19608168
AN - SCOPUS:77956188164
VL - 94
SP - 1296
EP - 1301
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 4
ER -