Pharmacokinetics of vaginal progesterone in pregnancy.

Publication/Presentation Date

9-1-2019

Abstract

BACKGROUND: Characterization of pharmacokinetics is lacking for vaginal progesterone in pregnancy. Dosing of vaginal progesterone for preterm birth prevention has been empirical. Owing to pregnancy-related changes in vaginal and uterine blood flow, hepatic metabolism, renal clearance, and endogenously elevated serum progesterone, studies outside of pregnancy may not be applicable. The lack of the pharmacokinetics profile of vaginally administered progesterone in pregnancy limits the ability to define the exposure-response relationship needed to optimize dosing, which has implications for its use in research and clinical care regarding management of short cervix, prevention of recurrent preterm birth, and prevention of recurrent miscarriage.

OBJECTIVE: This was a study to establish the feasibility of using serum progesterone to establish basic pharmacokinetic parameters of vaginal progesterone in pregnancy for preterm birth prevention.

STUDY DESIGN: This is a prospective study of 6 low-risk singletons at 18 0/7 to 23 6/7 weeks' gestation with body mass index 20-40. Exclusion criteria were current vaginitis, abnormal Pap smear, prescription medication use, cervical length ≤25 mm, prior preterm birth, and contraindication to progesterone. Participants received a single dose of 200 mg micronized vaginal progesterone and serum progesterone levels were evaluated every 2 hours from 0 to 12 hours and then 24 hours post dose. Primary outcome was concentration/time profile of serum progesterone.

RESULTS: Median (range) maternal age was 27 (21.5-33.3) years, median body mass index was 26.5 (23.3-29.0) kg/m

CONCLUSION: Unlike in nonpregnant individuals, administration of vaginal progesterone in pregnant individuals only minimally impacts systemic exposure. There is a limited trend of rising serum progesterone over baseline levels, with significant inter-individual variability. Serum progesterone is unlikely to be a good candidate for establishing pharmacokinetics or dosing of vaginal progesterone in pregnancy for preterm birth prevention.

Volume

221

Issue

3

First Page

1

Last Page

263

ISSN

1097-6868

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

31211965

Department(s)

Administration and Leadership

Document Type

Article

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