Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone

Archer, David F.; Fahy, George E.; Viniegra-Sibal, Amabel; Anderson, Freedolph D.; Snipes, Wallace; Foldesy, Robin G.

doi:10.1016/0002-9378(95)90268-6

Cited by 44 publications

(17 citation statements)

References 20 publications

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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). Although the pharmacokinetic characteristics of the drug have been studied in other populations previously, very little data are available describing these properties in Chinese population.…”

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.

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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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“…Vaginal application can result in sustained plasma concentrations (12)(13)(14). Experimental and clinical data also suggest that vaginal application provides significant levels of progesterone to the endometrial tissue, inducing secretory transformation (4,6,15,16).…”

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confidence: 99%

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

Blake

Norris

Dorfman

et al. 2010

Fertility and Sterility

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“…In 2011, the Food and Drug Administration (FDA) approved progesterone supplementation, specifically hydroxyprogesterone caproate injections, to reduce the risk of recurrent preterm birth in women with a singleton pregnancy who have a history of at least one prior spontaneous preterm delivery [70]. Despite these recommendations progesterone has not been approved for this use in Canada, and in this setting, its use is considered off label.…”

Section: Discussionmentioning

confidence: 99%

Progesterone supplementation for HIV-positive pregnant women on protease inhibitor-based antiretroviral regimens (the ProSPAR study): a study protocol for a pilot randomized controlled trial

Siou

Walmsley

Murphy

et al. 2016

Pilot Feasibility Stud

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BackgroundIn Canada, the majority of HIV-positive pregnant women receive combination antiretroviral therapy that includes a ritonavir-boosted protease inhibitor to prevent mother-to-child HIV transmission. However, protease inhibitor-based combination antiretroviral therapy has been associated with increased rates of preterm, low birth weight, and small for gestational age births. Our previous experimental findings demonstrate that protease inhibitor use during pregnancy is associated with decreased progesterone levels that correlate with fetal growth, and that progesterone supplementation can improve protease inhibitor-induced fetal growth restriction. We hypothesize that HIV-positive pregnant women who receive protease inhibitor-based combination therapy may also benefit from progesterone supplementation during pregnancy.Methods/designIn order to test this hypothesis, we have designed an open-label, multi-centre, randomized controlled (parallel group) pilot trial. The initial goal of this trial is to test feasibility and acceptability of our intervention. Forty HIV-positive pregnant women who are either on, or intending to start or switch to a boosted protease inhibitor-based combination antiretroviral regimen will be enrolled from six sites across Ontario, Canada. Twenty-five women will be randomized to self-administer natural progesterone (Prometrium, 200 mg) vaginally every night starting between gestational week 16 and 24 until week 36, and 15 women will be randomized to no intervention. While the participants and treating physicians will not be blinded, the laboratory personnel performing the biochemical and morphological evaluations will be blinded to ensure unbiased evaluation. The primary outcome of the pilot study is the feasibility of enrolment as measured by the recruitment rate and patient-reported reasons to decline participation. Secondary outcomes in participants include safety, acceptability, and adherence to progesterone supplementation.DiscussionGiven the safety of intravaginal progesterone and its current use in the general obstetrical population to prevent recurrent preterm delivery, this pilot study will provide data to determine the feasibility of a larger randomized controlled trial to assess the impact of this intervention on improving neonatal health in the context of HIV-positive pregnancies.Trial registrationClinicalTrials.gov, NCT02400021

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Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone

Cited by 44 publications

References 20 publications

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

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

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

Progesterone supplementation for HIV-positive pregnant women on protease inhibitor-based antiretroviral regimens (the ProSPAR study): a study protocol for a pilot randomized controlled trial

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