Atosiban in the Management of Preterm Labour

Fullerton, Gail; Black, Mairead; Shetty, Ashalatha; Bhattacharya, Sohinee

doi:10.4137/cmwh.s5125

Cited by 7 publications

(9 citation statements)

References 33 publications

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“…Atosiban has been shown to significantly reduce uterine contractions during PTB and delay labor by up to 48 h, without conferring significant maternal, fetal, or neonatal adverse effects [8,78,79]. One meta-analysis and multiple other studies have found no significant differences in rates of delivery at 48 h when comparing atosiban with a placebo, betamimetics, or calcium channel blockers (CCBs) [16,80,81]. Data are not available to suggest atosiban improves neonatal outcomes, but its lower discontinuation rate and safer side effect profile have led some studies to conclude that atosiban is preferable to betamimetics [16,80,81].…”

Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

“…One meta-analysis and multiple other studies have found no significant differences in rates of delivery at 48 h when comparing atosiban with a placebo, betamimetics, or calcium channel blockers (CCBs) [16,80,81]. Data are not available to suggest atosiban improves neonatal outcomes, but its lower discontinuation rate and safer side effect profile have led some studies to conclude that atosiban is preferable to betamimetics [16,80,81]. Like other tocolytic agents, long-term maintenance therapy with atosiban has generally not been shown to delay PTB beyond 48 h, and a meta-analysis suggested maintenance therapy was associated with a significantly higher incidence of injection site reaction when compared with a placebo [9,81].…”

Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

“…Data are not available to suggest atosiban improves neonatal outcomes, but its lower discontinuation rate and safer side effect profile have led some studies to conclude that atosiban is preferable to betamimetics [16,80,81]. Like other tocolytic agents, long-term maintenance therapy with atosiban has generally not been shown to delay PTB beyond 48 h, and a meta-analysis suggested maintenance therapy was associated with a significantly higher incidence of injection site reaction when compared with a placebo [9,81]. One study found that, following successful initial intravenous administration of atosiban, continued subcutaneous therapy with atosiban reduced the need for subsequent intravenous atosiban therapy [82].…”

Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

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Landscape of Preterm Birth Therapeutics and a Path Forward

Coler

Shynlova

Boros-Rausch

et al. 2021

JCM

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Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to high-level care facilities. Globally, there is an unmet need for better tocolytic agents, particularly in low- and middle-income countries. Although most tocolytics, such as betamimetics and indomethacin, suppress downstream mediators of the parturition pathway, newer therapeutics are being designed to selectively target inflammatory checkpoints with the goal of providing broader and more effective tocolysis. However, the relatively small market for new PTB therapeutics and formidable regulatory hurdles have led to minimal pharmaceutical interest and a stagnant drug pipeline. In this review, we present the current landscape of PTB therapeutics, assessing the history of drug development, mechanisms of action, adverse effects, and the updated literature on drug efficacy. We also review the regulatory hurdles and other obstacles impairing novel tocolytic development. Ultimately, we present possible steps to expedite drug development and meet the growing need for effective preterm birth therapeutics.

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Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

Section: Oxytocin Antagonism: Hope For Atosibanmentioning

confidence: 99%

See 1 more Smart Citation

Landscape of Preterm Birth Therapeutics and a Path Forward

Coler

Shynlova

Boros-Rausch

et al. 2021

JCM

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“…Modifications of the native hormone structure, introduced in these peptides, are aimed at increasing their proteolytic stability and improving their pharmacokinetic characteristics. 12−14 Terlipressin differs from Lys 8 -vasopressin by increasing the peptide chain by three glycine residues at the N-terminal; thus, it is a prodrug of Lys 8 -vasopressin, converting into it with a half-life of about 6 h by gradual cleavage of glycine residues. 13,14 In atosiban and desmopressin, replacing the N-terminal cysteine residue with mercaptopropionic acid (Mpa) prevents their rapid enzymatic degradation by aminopeptidases and increases their half-life from minutes to several hours (Figure 1).…”

Section: ■ Introductionmentioning

confidence: 99%

Formation of a Disulfide Bridge on the Resin during Solid-Phase Synthesis of Terlipressin: Influence of the Boc-Protected and Free N-Terminal Amino Group

Avdeev,

Ovchinnikov,

Medvedev

et al. 2023

Org. Process Res. Dev.

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An industry-ready approach for the synthesis of terlipressin is developed: the entire peptide chain assembly and subsequent disulfide bond closure are carried out on a polymeric carrier with a specific precaution for the protection of the Nterminal α-amino group. The effect of various factors on the purity of crude disulfide was studied, and the solid-phase cyclization process was optimized. The designed approach has high fidelity and reproducibility and is applicable for a large-scale peptide synthesis (we show it up to 15 g of the pure product). Using molecular modeling, we have found that the state of the N-terminal amino group (free or protected) has a significant influence on the ability of two cysteine side chains to reach each other, paving the way to a rational choice of protecting groups in peptide synthesis.

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“…The presented study was conducted on atosiban (Figure ), which is a disulfide-containing cyclic octa-peptide that functions as an inhibitor of the hormones oxytocin and vasopressin and is used as a labor repressant (tocolytic) to halt premature labor. It is commercialized by Ferring Pharmaceuticals under the trade name Tractocile …”

Section: Introductionmentioning

confidence: 99%

Investigation of On-Resin Disulfide Formation for Large-Scale Manufacturing of Cyclic Peptides: A Case Study

Yang

Hansen

Badalassi

2020

Org. Process Res. Dev.

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Peptide molecules bearing disulfide moieties constitute an important category of therapeutics. The establishment of the disulfide structure plays a pivotal role in the production of those peptides. In-solution cyclization is generally adopted in industrial peptide production as a synthetic strategy to build disulfide from the linear deprotected precursor. This methodology is inherently limited by the relatively low productivity, considering the minimizing intermolecular oligomerization by dilution of the overall concentration of the reaction. Alternatively, the disulfide bond could be established from the thiol-protected building blocks directly on the solid support. On-resin disulfide construction was pursued for atosiban process development. Protected linear atosiban resin was treated with I 2 /dimethylformamide (DMF), and the target disulfide was built rapidly and quantitatively within 30 min. The effects of the resin linker and thiol-protecting groups were tested by utilizing Sieber resin, Rink amide resin, and Ramage resin as solid supports and Cys(Trt)/Cys(Acm) as building blocks. The I 2 equivalence, as a potential critical process parameter, was subjected to a proven acceptable range (PAR) study to facilitate the envisioned large-scale manufacturing. Although there was rapid and complete disulfide formation on the solid support in all tested combinations of resin and thiol-protecting groups, a reduction of the disulfide was observed in the processes of a certain peptidyl resin cleavage/global deprotection. A dedicated investigation revealed that hydrosilane, employed as a cation scavenger in peptide synthesis, is responsible for the disulfide degradation in the presence of trifluoroacetic acid (TFA). Eliminating silane from the TFA cleavage solution or subtly controlling its equivalence could effectively suppress the nocuous disulfide reduction in this process. In summary, on-resin disulfide cyclization has been verified to be a viable strategy for atosiban industrial production by this study.

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Atosiban in the Management of Preterm Labour

Cited by 7 publications

References 33 publications

Landscape of Preterm Birth Therapeutics and a Path Forward

Landscape of Preterm Birth Therapeutics and a Path Forward

Formation of a Disulfide Bridge on the Resin during Solid-Phase Synthesis of Terlipressin: Influence of the Boc-Protected and Free N-Terminal Amino Group

Investigation of On-Resin Disulfide Formation for Large-Scale Manufacturing of Cyclic Peptides: A Case Study

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