Effect of 17-α hydroxyprogesterone caproate on the production of tumor necrosis factor-α and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants

Patel, Sanjeet G.; Li, A.; Goodwin, T. Murphy; Brower, M.; Blitz, Matthew J.; Minoo, Parviz; Felix, Janine F.; Lee, R. H.

doi:10.1038/jp.2010.23

Cited by 6 publications

(6 citation statements)

References 37 publications

(35 reference statements)

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“…Further, while vaginal progesterone has been shown to have anti-inflammatory effects at the choriodecidual interface in a murine model, sub-cutaneous 17-OHPC did not [33]. Nor did 17-OHPC repress basal or LPS-stimulated TNFα or COX-2 production in human myometrial explants [34]. In terms of in vitro contractility studies on strips of human myometrium, 17-OHPC enhanced oxytocin-induced contractions in one study [35] and to have no effect in several other studies [36][37][38].…”

Section: Discussionmentioning

confidence: 86%

LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation

Zöllner

Howe

Edey

et al. 2020

Shock

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Our previous work has shown that pregnancy exacerbates the hypotensive response to both infection and LPS. The high levels of progesterone (P4) associated with pregnancy have been suggested to be responsible for the pregnancy-induced changes in the cardiovascular response to infection. Here, we test the hypothesis that P4 supplementation exacerbates the hypotensive response of the maternal cardiovascular to LPS. Female CD1 mice had radiotelemetry probes implanted to measure haemodynamic function non-invasively and were time-mated. From day 14 of pregnancy, mice received either 10mg of P4 or vehicle alone per day and on day 16, intraperitoneal LPS (10µg of serotype 0111:B4) was injected. In two identically treated cohorts of mice, tissue and serum (for RNA, protein studies) were collected at 6 and 12 hours. Administration of LPS resulted in a fall in blood pressure in vehicle treated, but not P4 supplemented mice. This occurred with similar changes in the circulating levels of cytokines, vasoactive factors and in both circulating and tissue inflammatory cell numbers, but with reduced left ventricular expression of cytokines in P4-supplemented mice. However, left ventricular expression of markers of cardiac dysfunction and apoptosis were similar. This study demonstrates that P4 supplementation prevented LPS-induced hypotension in pregnant mice in association with reduced myocardial inflammatory cytokine gene expression. These observations suggest that rather than being detrimental, P4 supplementation has a protective effect on the maternal cardiovascular response to sepsis.

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Section: Discussionmentioning

confidence: 86%

LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation

Zöllner

Howe

Edey

et al. 2020

Shock

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“…One study evaluated the effects of 17OHPC on human myometrial tissue and the production of TNF-α (an inflammatory cytokine) and the expression of COX-2 (an enzyme that mediates the production of prostaglandins). The authors found no difference in the tissues that had been treated with 17OHPC versus those that had not [25]. Similarly, 17OHPC does not appear to have an effect on uterine contractility.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

17-α Hydroxyprogesterone Caproate for the Prevention of Preterm Birth

Gupta

Roman

2012

Womens Health (Lond Engl)

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17 α hydroxyprogesterone caproate is a synthetic form of the natural progestin 17-α hydroxyprogesterone that is US FDA approved for the prevention of recurrent spontaneous preterm birth in women with a history of a prior singleton preterm birth. For women with a history of a prior spontaneous preterm birth between 20 weeks and 36 weeks and 6 days of gestation, the use of 17-α hydroxyprogesterone caproate has been shown to reduce the risk of recurrent preterm birth by more than 30%. This medication is the only drug currently FDA approved for the prevention of preterm birth, and it is the first drug the FDA has approved for use exclusively during pregnancy in approximately 15 years.

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“…1 Despite the widespread use of this agent, very little pharmacologic information exists as to the proper dosing regimen or the mechanism of action of the drug. 18,19, 20, 21, 22, 23 The currently utilized regimen of 250 mg injected intramuscularly weekly is empiric. Our study indicates a wide inter-individual variation in the pharmacology of 17-OHPC.…”

Section: Commentmentioning

confidence: 99%

Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation

Caritis

Sharma

Venkataramanan

et al. 2011

American Journal of Obstetrics and Gynecology

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Objective To define the pharmacokinetic (PK) parameters of 17-hydroxyprogesterone caproate (17-OHPC) in multifetal gestation. Study Design Blood was obtained at 24–28 weeks and at 32–35 weeks in 97 women with twin and 26 women with triplet gestation receiving 17-OHPC. Six of the women with twins had daily blood sampling for 7 days between 24 and 28 weeks and PK parameters were estimated using noncompartmental analysis. Modeling was applied to estimate the population parameters and to simulate various treatment scenarios. Results The apparent half-life of 17-OHPC was 10 days. BMI significantly impacted 17-OHPC concentrations but fetal number and parity did not. Apparent clearance was significantly greater in African American than in Caucasian women (p = 0.025). Conclusions This is the first pharmacokinetic analysis of 17-OHPC in pregnant women. Determination of half life, covariates affecting plasma 17-OHPC concentrations and modeling of drug behavior provide insights into this drug’s pharmacology during multifetal pregnancy.

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Effect of 17-α hydroxyprogesterone caproate on the production of tumor necrosis factor-α and the expression of cyclooxygenase-2 in lipopolysaccharide-treated gravid human myometrial explants

Cited by 6 publications

References 37 publications

LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation

LPS-Induced Hypotension in Pregnancy: The Effect of Progesterone Supplementation

17-α Hydroxyprogesterone Caproate for the Prevention of Preterm Birth

Pharmacokinetics of 17-hydroxyprogesterone caproate in multifetal gestation

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