Wirksamkeit und Sicherheit von Atosiban vs. pulsatiler Applikation von Fenoterol bei der Behandlung vorzeitiger Wehen

Nonnenmacher, A; Hopp, H; Dudenhausen, Joachim

doi:10.1055/s-0029-1225640

Cited by 12 publications

(6 citation statements)

References 8 publications

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“…Finally, fenoterol has been investigated and shown clinically to inhibit uterine activity, by up to 30%, in women with OT-induced labor [ 45 ]. While fenoterol has been shown to be an effective agent for treatment of preterm labor, its use as a tocolytic in women was terminated due to maternal adverse effects [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

et al. 2015

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The uterine myometrium (UT-myo) is a therapeutic target for preterm labor, labor induction, and postpartum hemorrhage. Stimulation of intracellular Ca2+-release in UT-myo cells by oxytocin is a final pathway controlling myometrial contractions. The goal of this study was to develop a dual-addition assay for high-throughput screening of small molecular compounds, which could regulate Ca2+-mobilization in UT-myo cells, and hence, myometrial contractions. Primary murine UT-myo cells in 384-well plates were loaded with a Ca2+-sensitive fluorescent probe, and then screened for inducers of Ca2+-mobilization and inhibitors of oxytocin-induced Ca2+-mobilization. The assay exhibited robust screening statistics (Z´ = 0.73), DMSO-tolerance, and was validated for high-throughput screening against 2,727 small molecules from the Spectrum, NIH Clinical I and II collections of well-annotated compounds. The screen revealed a hit-rate of 1.80% for agonist and 1.39% for antagonist compounds. Concentration-dependent responses of hit-compounds demonstrated an EC50 less than 10μM for 21 hit-antagonist compounds, compared to only 7 hit-agonist compounds. Subsequent studies focused on hit-antagonist compounds. Based on the percent inhibition and functional annotation analyses, we selected 4 confirmed hit-antagonist compounds (benzbromarone, dipyridamole, fenoterol hydrobromide and nisoldipine) for further analysis. Using an ex vivo isometric contractility assay, each compound significantly inhibited uterine contractility, at different potencies (IC50). Overall, these results demonstrate for the first time that high-throughput small-molecules screening of myometrial Ca2+-mobilization is an ideal primary approach for discovering modulators of uterine contractility.

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Section: Discussionmentioning

confidence: 99%

High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

et al. 2015

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“…Of interest is a prospective, randomised study from Germany 55 on 105 pregnant women between 24 + 0 to 33 + 6 weeks of pregnancy in which the pulsatile application of fenoterol was compared to atosiban at a standard dosage. This revealed no significant differences with regard to prolongation of pregnancy by 48 hours (79.8 vs. 86.3%) and by 7 days (66.7 vs. 78.4%).…”

Section: Oxytocin Receptor Antagonists (Atosiban)mentioning

confidence: 99%

Acute Tocolysis – a Critical Analysis of Evidence-Based Data

Rath

Kehl

2018

Geburtshilfe Frauenheilkd

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Tocolysis is among the most common obstetric measures. The objective is to prolong the pregnancy by at least 48 hours to complete foetal lung maturation and for the in-utero transfer of the pregnant woman to a perinatal centre. The indication for tocolysis is regular, premature contractions (≥ 4/20 min) and a dynamic shortening of the cervical length/cervical opening between 22 + 0 to 33 + 6 weeks of pregnancy. In this connection, the cervical length measured on ultrasound and the determination of biomarkers in the cervicovaginal secretions can be important decision-making aids. Beta sympathomimetics should no longer be used due to the high rate of severe maternal adverse effects. Given controversial data, magnesium sulphate is no longer recommended for tocolysis in current guidelines. Atosiban is as effective for prolonging pregnancy as beta sympathomimetics and nifedipine, has the lowest rate of maternal adverse effects, but also the highest drug costs. Nifedipine and indomethacin are recommended in international guidelines for acute tocolysis, however there are indications of increased neonatal morbidity following indomethacin. Current problems are, above all, the lack of randomised, controlled comparative and placebo-controlled studies, the data which are controversial to some extent, and the insufficient evidence of tocolytics to significantly improve the neonatal outcome.

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“…The 11 phase III controlled clinical trials were assessed. (20-30) High risk of performance and detection biases was identified for 5 open-label studies (20,21,23,24,28). For the remaining studies, low or indeterminate risk of selection, performance, detection, attrition reporting and other forms of biases were found.…”

Section: Risk Of Biasesmentioning

confidence: 99%

“…Delivery delay of more than 7 days: 7 relevant studies were identified for this comparison (20,21,(23)(24)(25)(26)29) with a total of 1305 randomized patients; a network meta-analysis was performed (Table 3). No statistically significant differences were found between atosiban and fenoterol (RR = 1.18; 95% CI: 0.71-1.95, moderate certainty), nifedipine (RR = 1.06; 95% CI: 0.82-1.37, moderate certainty) and terbutaline (RR = 1.37; 95% CI: 0.99-1.89, low As for the comparison with placebo, the headto-head study (22) provides a composite result together with the outcome of not requiring additional tocolytic agents at 7 days.…”

Section: Effectivenessmentioning

confidence: 99%

“…No significant differences were found between fenoterol, nifedipine and terbutaline. Given the (20,21,23,26,28), for a total of 588 randomized patients; a network meta-analysis was performed (Table 6). Statistically significant differences were found between atosiban and fenoterol (RR = 0.16; 95% CI: 0.08-0.31, moderate certainty), nifedipine (RR = 0.48; 95% CI: 0.3-0.78, moderate certainty) and terbutaline (RR = 0.44; 95% CI: 0.28-0.71, moderate certainty).…”

Section: Safetymentioning

confidence: 99%

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Eficacia y seguridad de atosiban en mujeres gestantes con diagnóstico de amenaza de parto pretérmino: revisión sistemática de la literatura con metaanálisis en red

Salazar-Castelblanco

Restrepo-Jiménez

Lasalvia

et al. 2018

Rev. Colomb. Obstet. Ginecol.

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Objetivo: evaluar la eficacia y seguridad de atosiban en gestantes con amenaza de parto pretérmino comparado con nifedipino, indometacina, terbutalina, fenoterol y placebo.Materiales y métodos: se realizó una revisión sistemática de la literatura en ocho bases de datos electrónicas (Medline, Central, Embase, entre otras), mediante términos de búsqueda libres y estandarizados. Los desenlaces evaluados incluyeron tiempo de retardo del parto, mortalidad neonatal, proporción de eventos adversos maternos y proporción de complicaciones neonatales. Se evaluó la calidad de la evidencia por estudio y para el cuerpo de evidencia, y se sintetizó la información mediante metaanálisis, cuando fue posible; de lo contrario, se resumió de forma narrativa.Resultados: se incluyeron once estudios. Atosiban no mostró diferencias estadísticamente significativas en retardo del parto contra otros uteroinhibidores. Mostró menor mortalidad neonatal que la indometacina (RR = 0,21; IC 95 %: 0,05 a 0,92), y menor proporción de eventos adversos maternos totales que el fenoterol (RR = 0,16; IC 95 %: 0,08 a 0,31), el nifedipino (RR = 0,48; IC 95 %: 0,3 a 0,78) y la terbutalina (RR = 0,44; IC 95 %: 0,28 a 0,71).Conclusiones: atosiban tiene una eficacia similar para retardar el parto ante la amenaza de un parto pretérmino con otros comparadores (certeza moderada), con ventajas frente a indometacina en mortalidad neonatal (certeza baja) y frente a fenoterol, nifedipino y terbutalina en eventos adversos maternos (certeza moderada).

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Wirksamkeit und Sicherheit von Atosiban vs. pulsatiler Applikation von Fenoterol bei der Behandlung vorzeitiger Wehen

Abstract: Atosiban was comparable in clinical effectiveness and was associated with fewer maternal and fetal adverse effects, so that fenoterol cannot be recommended. Completion of tocolytic therapy 12 hours after arrest of preterm labour is effective and associated with a short mean duration.

Cited by 12 publications

References 8 publications

High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

High-Throughput Screening of Myometrial Calcium-Mobilization to Identify Modulators of Uterine Contractility

Acute Tocolysis – a Critical Analysis of Evidence-Based Data

Eficacia y seguridad de atosiban en mujeres gestantes con diagnóstico de amenaza de parto pretérmino: revisión sistemática de la literatura con metaanálisis en red

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