Sinapultide

(USAN, rINN)
Synonyms: ATI-01; Sinapultida; Sinapultidum.
Cyrillic synonym: Синапультид.

💊 Chemical information

CAS — 138531-07-4.

Description.

Sinapultide is a synthetic peptide that mimics the actions of human surfactant protein B, an important constituent of natural pulmonary surfactant compounds.

💊 Adverse Effects and Precautions

Surfactant therapy may be associated with an increased risk of pulmonary haemorrhage, especially in more premature infants. Therapy should only be given where there are adequate facilities for ventilation and monitoring. Rapid chest expansion and improvement of oxygenation may follow successful treatment, and peak ventilatory pressure and inspired oxygen concentration may need to be reduced promptly to avoid the risk of pneumothorax and hyperoxaemia. A transient decrease in brain electrical activity has been reported in neonates given surfactant but its significance is unknown. Transient bradycardia has also been reported. Giving surfactant has occasionally been associated with obstruction of the endotracheal tube by mucus. However, neonates who do develop moderate or severe pulmonary haemorrhage after surfactant therapy are at increased risk of death or short-term morbidity.5 Haemodynamic changes associated with surfactant therapy or consequent pulmonary haemorrhage may also predispose premature infants to intracranial (periventricular) haemorrhage.5,6 Early preventive use of surfactant in very low birthweight infants may be associated with a poorer neurodevelopmental outcome,7 although a long-term follow-up study8 of premature infants born in the surfactant era concluded that these children had similar neurodevelopmental outcomes to such children born before the introduction of surfactant therapy. Decreased brain electrical activity has been reported after surfactant treatment.9 The rate of instillation of surfactant may be significant: one study,10 in which the apparatus was adapted so that mechanical ventilation could continue while giving surfactant, found that rapid instillation over a 5-minute period provoked a transient increase in cerebral blood flow velocity associated with an increase in carbon dioxide tension, compared with slow instillation over 15 minutes. Although the authors acknowledged that such changes were likely to be related to several factors, particularly the type of surfactant, they recommended that, until further data were available, instillation should take place slowly, over at least 15 to 20 minutes.
1. Raju TNK, Langenberg P. Pulmonary hemorrhage and exogenous surfactant therapy: a metaanalysis. J Pediatr 1993; 123: 603–10
2. Majeed-Saidan MA, et al. Pulmonary haemorrhage in lowbirthweight babies. Lancet 1993; 341: 120
3. Rogers D. Pulmonary haemorrhage, surfactant, and low-birthweight babies. Lancet 1993; 341: 698
4. Pappin A, et al. Extensive intraalveolar pulmonary hemorrhage in infants dying after surfactant therapy. J Pediatr 1994; 124: 621–6
5. Pandit PB, et al. Outcome following pulmonary haemorrhage in very low birthweight neonates treated with surfactant. Arch Dis Child Fetal Neonatal Ed 1999; 81: F40–F44
6. Gunkel JH, Banks PLC. Surfactant therapy and intracranial hemorrhage: review of the literature and results of new analyses. Pediatrics 1993; 92: 775–86
7. Vaucher YE, et al. Outcome at twelve months of adjusted age in very low birthweight infants with lung immaturity: a randomized placebo-controlled trial of human surfactant. J Pediatr 1993; 122: 126–32
8. D’Angio CT, et al. Longitudinal, 15-year follow-up of children born at less than 29 weeks’ gestation after introduction of surfactant therapy into a region: neurologic, cognitive, and educational outcomes. Pediatrics 2002; 110: 1094–1102
9. Hellström-Westas L, et al. Cerebroelectrical depression following surfactant treatment in preterm neonates. Pediatrics 1992; 89: 643–7
10. Saliba E, et al. Instillation rate effects of Exosurf on cerebral and cardiovascular haemodynamics in preterm neonates. Arch Dis Child 1994; 71: F174–8.

💊 Uses and Administration

Pulmonary surfactants are compounds with surface active properties similar to those natural substances in the lung that help to maintain the patency of the airways by reducing the surface tension of pulmonary fluids. Exogenous pulmonary surfactants are used in the treatment of neonatal respiratory distress syndrome in premature infants, and may also be given for prevention in infants considered to be at risk of developing the syndrome. Doses vary, but most pulmonary surfactants are given in recommended doses of 100 to 200 mg phospholipids per kg birth-weight; a suggested dose for colfosceril palmitate is 67.5 mg/kg. For the treatment of overt neonatal respiratory distress syndrome, the initial dose is given as soon as possible after diagnosis, while for prevention it is given as soon as possible after birth. It is given as a suspension via an endotracheal tube to intubated neonates receiving mechanical ventilation. Manufacturers may recommend regimens with or without disconnection from the ventilator. Repeat doses may be given if necessary, although the number of doses and the dosage interval varies. Pulmonary surfactants have also been tried in bronchopulmonary dysplasia in premature infants, meconium aspiration syndrome in newborn infants, and acute respiratory distress syndrome in adults. A similar compound lusupultide is also under investigation for aspiration pneumonitis.

Acute respiratory distress syndrome.

Pulmonary surfactants have been investigated for acute respiratory distress syndrome. In adults, they have been given by intrabronchial instillation1 or nebulisation2-4 but results have been largely disappointing. Sequential bronchopulmonary segmental lavage with a synthetic surfactant has also been tried5 and appeared to be well tolerated. Endotracheal poractant alfa moderately improved oxygenation in some children with severe acute respiratory distress syndrome secondary to pulmonary or systemic disease.6
1. Haslam PL, et al. Surfactant replacement therapy in late-stage adult respiratory distress syndrome. Lancet 1994; 343: 1009–11
2. do Campo JL, et al. Natural surfactant aerosolisation in adult respiratory distress syndrome. Lancet 1994; 344: 413–14
3. Weg JG, et al. Safety and potential efficacy of an aerosolized surfactant in human sepsis-induced adult respiratory distress syndrome. JAMA 1994; 272: 1433–8
4. Anzueto A, et al. Aerosolized surfactant in adults with sepsisinduced respiratory distress syndrome. N Engl J Med 1996; 334: 1417–21
5. Wiswell TE, et al. Bronchopulmonary segmental lavage with Surfaxin (KL -Surfactant) for acute respiratory distress syndrome. Am J Respir Crit Care Med 1999; 160: 1188–95
6. López-Herce J, et al. Surfactant treatment for acute respiratory distress syndrome. Arch Dis Child 1999; 80: 248–52.

Drowning.

Reference to the use of colfosceril palmitate in the management of a 9-year-old rescued after near drowning.1
1. McBrien M, et al. Artificial surfactant in the treatment of near drowning. Lancet 1993; 342: 1485–6.

Meconium aspiration syndrome.

Meconium aspiration syndrome produces respiratory distress in infants born at term or later and is a consequence of disturbances of the pulmonary surfactant system. Bolus doses of exogenous pulmonary surfactant are of benefit in some ventilated infants, although lung lavage with dilute surfactant is also under investigation.1 Results from a pilot study2 of beractant as a tracheobronchial lavage fluid for the treatment of infants with severe meconium aspiration syndrome were promising, and a small comparative trial3 found that bronchoalveolar lavage with diluted beractant, with or without intravenous dexamethasone, significantly improved oxygenation in neonates when compared with standard therapy. Systematic review4 of 4 randomised controlled trials evaluating the effect of pulmonary surfactants also found encouraging results, although comparison with other established treatments for meconium aspiration syndrome remains to be done.
1. Dargaville PA, Mills JF. Surfactant therapy for meconium aspiration syndrome: current status. Drugs 2005; 65: 2569–91
2. Lam BCC, Yeung CY. Surfactant lavage for meconium aspiration syndrome: a pilot study. Pediatrics 1999; 103: 1014–18
3. Salvia-Roigés MD, et al. Efficacy of three treatment schedules in severe meconium aspiration syndrome. Acta Paediatr 2004; 93: 60–5
4. El Shahed AI, et al. Surfactant for meconium aspiration syndrome in full term/near term infants. Available in The Cochrane Database of Systematic Reviews; Issu
3. Chichester: John Wiley; 2007 (accessed 13/06/08).

💊 Preparations

Proprietary Preparations

Arg.: Baby Fact B; Exosurf†; Natsurf†; Surfactante B; Survanta; Austral.: Curosurf; Exosurf; Survanta; Austria: Alveofact†; Curosurf; Exosurf; Survanta; Belg.: Alvofact†; Curosurf; Survanta; Braz.: Alveofact; Curosurf; Exosurf†; Survanta; Canad.: BLES; Exosurf†; Survanta; Chile: Exosurf†; Survanta; Cz.: Alveofact†; Curosurf; Exosurf†; Survanta; Denm.: Curosurf; Fin.: Curosurf; Fr.: Curosurf; Survanta; Ger.: Alveofact; Curosurf; Survanta; Gr.: Alvofact; Curosurf; Exosurf†; Survanta; Hong Kong: Exosurf†; Survanta; Hung.: Curosurf; Survanta; Indon.: Survanta; Irl.: Curosurf; Exosurf†; Israel: Curosurf; Exosurf†; Infasurf; Ital.: Curosurf; Exosurf†; Jpn: Surfacten; Malaysia: Survanta; Mex.: Exosurf; Survanta; Neth.: Alvofact†; Curosurf; Exosurf†; Survanta; Norw.: Curosurf; Survanta-Vent; NZ: Curosurf; Survanta; Philipp.: Survanta; Pol.: Alveofact; Curosurf; Survanta; Port.: Curosurf; Rus.: Curosurf (Куросурф); S.Afr.: Curosurf; Survanta; Singapore: Survanta; Spain: Curosurf; Survanta; Swed.: Curosurf; Survanta-Vent†; Switz.: Curosurf; Survanta; Thai.: Curosurf; Survanta; UK: Curosurf; Survanta; USA: Curosurf; Exosurf†; Infasurf; Survanta; Venez.: Survanta.
Published May 08, 2019.