Placental passage of the oxytocin antagonist atosiban

Valenzuela, Guillermo J.; Craig, Jan; Bernhardt, Mark D.; Holland, Mary L.

doi:10.1016/0002-9378(95)91497-8

Cited by 52 publications

(21 citation statements)

References 7 publications

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“…Drug concentrations in the fetal circulation do not increase with longer infusion rates, suggesting that the drug does not accumulate in the fetus 29. Atosiban does not significantly alter maternal or fetal cardiovascular parameters when it is administered to late pregnant sheep 30.…”

Section: Fetal Effectsmentioning

confidence: 95%

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Management of preterm labor: atosiban or nifedipine?

Heus

Mulder²,

Visser³

2010

IJWH

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Preterm birth is strongly associated with neonatal death and long-term neurological morbidity. The purpose of tocolytic drug administration is to postpone threatening preterm delivery for 48 hours to allow maximal effect of antenatal corticosteroids and maternal transportation to a center with specialized neonatal care facilities. There is uncertainty about the value of atosiban (oxytocin receptor antagonist) and nifedipine (calcium channel blocker) as first-line tocolytic drugs in the management of preterm labor. For nifedipine, concerns have been raised about unproven safety, lack of placebo-controlled trials, and its off-label use. The tocolytic efficacy of atosiban has also been questioned because of a lack of reduction in neonatal morbidity. This review discusses the available evidence, the pros and cons of either drug and aims to provide information to support a balanced choice of first-line tocolytic drug: atosiban or nifedipine?

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Section: Fetal Effectsmentioning

confidence: 95%

“…Atosiban crosses the placenta in an average fetal versus maternal ratio of 0.124 29. Drug concentrations in the fetal circulation do not increase with longer infusion rates, suggesting that the drug does not accumulate in the fetus 29.…”

Section: Fetal Effectsmentioning

confidence: 99%

Management of preterm labor: atosiban or nifedipine?

Heus

Mulder²,

Visser³

2010

IJWH

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“…Downregulation of the oxytocin receptors with an apparent decrease in myometrial oxytocin receptor numbers [22] and postreceptor effects are other possible actions of TT-235. Currently only one oxytocin antagonist, atosiban (Ortho-McNeil Pharmaceuticals, Raritan, N.J., USA), is in clinical trials [11][12][13]. It was important to test TT-235 in a primate model because compounds that show antioxytocic properties in one animal species may have different relative activities in other species or even turn out to have oxytocic properties.…”

Section: Discussionmentioning

confidence: 99%

“…Oxytocin antagonists are being developed as potential tocolytics to treat preterm labor, because this is still the number one cause of fetal mortality and morbidity in developed countries [11][12][13]. They have been investigated in various animal experimental models with the ultimate goal of applying them in the clinical area.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Oxytocin and Oxytocin Antagonist Metabolism in the Plasma of Pregnant Humans and Baboons

Song¹,

Pak³

et al. 2002

Gynecol Obstet Invest

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Oxytocin antagonists may be useful in inhibiting the uterine contractions of preterm labor. One such compound is TT-235 (previously referred to as Antag III). The purpose of this study was to compare the resistance of TT-235 and oxytocin to enzymatic degradation by oxytocinase in the blood of humans and baboons during their 3rd trimester of pregnancy. Blood samples from pregnant women and baboons not in labor were incubated in vitro with known amounts of oxytocin and TT-235. Samples were collected at 0, 15, 30, 45, and 60 min for oxytocin analysis and at 0, 10, 60, and 360 min for TT-235 analysis. Oxytocin was analyzed by radioimmunoassay after extraction, while TT-235 was analyzed by radioreceptor assay. In human blood, oxytocin was readily metabolized with >83% disappearance over the 60-min incubation period. In contrast, TT-235 was stable up to 360 min of incubation. In the baboon, oxytocin did not diminish over the 60-min incubation period. The level of TT-235 was similar to that in human blood without change over 360 min of incubation. This study suggests (1) that in contrast to blood from pregnant humans, blood from pregnant baboons lacks oxytocinase at least in vitro and (2) that TT-235 is resistant to enzymatic degradation by human blood, implying that this oxytocin antagonist may have a prolonged activity in vivo in humans.

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“…In late-gestation sheep, the administration of atosiban for 1 hour failed to induce fetomaternal cardiovascular changes 92. IV atosiban (300 μg/min) used in women scheduled for elective cesarean section demonstrated no significant effect on the umbilical cord blood gases, and maternal hematocrit 93. In contrast Blea et al found that in pregnant ewes, IV nifedipine was associated with fetal hypoxia and acidosis 94.…”

Section: Adverse Effects Of Tocolyticsmentioning

confidence: 97%

Critical appraisal and clinical utility of atosiban in the management of preterm labor

Sanu

Lamont

2010

TCRM

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Preterm birth is the major cause of perinatal morbidity and mortality in the developed world, and spontaneous preterm labor is the commonest cause of preterm birth. Interventions to treat women in spontaneous preterm labor have not reduced the incidence of preterm births but this may be due to increased risk factors, inclusion of births at the limits of viability, and an increase in the use of elective preterm birth. The role of antibiotics remains unproven. In the largest of the randomized controlled trials, evaluating the use of antibiotics for the prevention of preterm births in women in spontaneous preterm labor, antibiotics against anaerobes and bacterial vaginosis-related organisms were not included, and no objective evidence of abnormal genital tract flora was obtained. Atosiban and nifedipine are the main tocolytic agents used to treat women in spontaneous preterm labor, but atosiban is the tocolytic agent with the fewest maternal – fetal side effects. A well conducted randomized controlled trial comparing atosiban with nifedipine for their effectiveness and safety is needed.

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Placental passage of the oxytocin antagonist atosiban

Cited by 52 publications

References 7 publications

Management of preterm labor: atosiban or nifedipine?

Management of preterm labor: atosiban or nifedipine?

Comparison of Oxytocin and Oxytocin Antagonist Metabolism in the Plasma of Pregnant Humans and Baboons

Critical appraisal and clinical utility of atosiban in the management of preterm labor

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