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; Dorfman, Sally Faith; Longstreth, James; Yankov, Vladimir

doi:10.1016/j.fertnstert.2009.06.014

Cited by 33 publications

(16 citation statements)

References 30 publications

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“…The estimates for Crinone total systemic exposure by Blake et al (1) are substantially lower than previously reported elsewhere (2) (Crinone label). In the study by Blake's group (1), the mean area under the curve (AUC 0-24 ) ( Table 2) was 81 ng-h/ mL and 264 ng-h/mL after single-dose and multidose administration, respectively.…”

contrasting

confidence: 60%

Progesterone pharmacokinetic study

Abrams¹,

Berger

2010

Fertility and Sterility

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contrasting

confidence: 60%

Progesterone pharmacokinetic study

Abrams¹,

Berger

2010

Fertility and Sterility

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“…Given lack of endogenous P in programmed endometrial preparation cycles, we were particularly concerned with selecting a vaginal P preparation, dosage, and frequency that would provide adequate trough levels while maintaining patient safety and adherence. In a direct comparison of the two available micronized vaginal P preparations approved for ART, Endometrin 100 mg at doses of both twice and three times daily achieved higher maximum serum concentrations, produced greater systemic exposure, and achieved steady state (trough concentrations >10 ng/mL) more rapidly than daily Crinone 90 mg, which did not reach steady state by 5 days (39). That said, Crinone is the only vaginal P preparation with an FDA-approved indication for replacement, and the approved dose (90 mg twice daily) is twice that recommended for supplementation (90 mg once daily) (40).…”

Section: Discussionmentioning

confidence: 97%

Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial

Devine

Richter

Widra

et al. 2018

Fertility and Sterility

112

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“…Several studies on its pharmacokinetic properties have been carried out in healthy reproductive aged female subjects (Nahoul et al, 1993; Blake et al, 2010) and post-menopausal women (Levine and Watson, 2000). Following vaginal administration, peak plasma concentration ( C max ) were reached approximately 5–7 h. Vaginal application can result in sustained plasma concentrations (Kimzey et al, 1991; Norman et al, 1991; Archer et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

Chen

et al. 2017

Front. Pharmacol.

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Objective: A generic vaginal progesterone gel has recently been developed in China. Little is known about its pharmacokinetic properties in Chinese subjects. The purpose of our study was to investigate the pharmacokinetics of three forms of vaginal progesterone gel (test formulations at 4 and 8% strength vs. a reference formulation: Crinone 8%) in Chinese healthy post-menopausal women.Methods: This study consisted of two parts study. The part 1 study was a single-center, open-label, 3-period study. Twelve healthy post-menopausal women were to evaluate the safety and pharmacokinetics of 45 mg vaginal progesterone gel (Test 4%) following single dose and multiple doses administered once every other day (q.o.d.) for six times or once daily (q.d.) for 6 days. The part 2 study was a randomized, open-label, 3-stage crossover study. Twelve post-menopausal women received 90 mg vaginal progesterone gel (Test 8%) or 90 mg Crinone (Reference 8%) following single dose and multiple doses (q.o.d. or q.d.). Plasma concentrations of progesterone were measured up to 72 h by using a validated liquid chromatography tandem-mass spectrometry method. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax) and area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUC0-t) and extrapolated to infinity (AUC0-∞) were compared by an analysis of variance using log-transformed data.Results: Totally 24 subjects were enrolled in and completed the study. Following single dose, The geometric mean Cmax values for Test 4%, Test 8%, and Crinone 8% were 6.35, 10.34, 10.45 ng/mL, and their geometric mean AUC0-t (AUC0-∞) were 113.73 (118.00), 169.39 (173.98), and 190.07 (201.13) ng⋅h/mL, respectively. The mean T1/2 values of progesterone were 11.00, 10.92, and 11.40 h, respectively. For 8% test formulation vs. reference, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 78.32–124.85%, 54.31–146.24%, and 53.64–137.75, respectively. The most frequent adverse events were increased vaginal secretions, most of which were of mild intensity and considered related to treatment.Conclusion: Results with single and multiple doses of vaginal progesterone gel suggest similar pharmacokinetics properties between test formulations and Crinone 8%. Overall, vaginal progesterone gel was well tolerated.

show abstract

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

Cited by 33 publications

References 30 publications

Progesterone pharmacokinetic study

Progesterone pharmacokinetic study

Vitrified blastocyst transfer cycles with the use of only vaginal progesterone replacement with Endometrin have inferior ongoing pregnancy rates: results from the planned interim analysis of a three-arm randomized controlled noninferiority trial

Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

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