SUMMARY Intravenous indomethacin was given to 36 neonates with a patent ductus arteriosus who where receiving ventilatory support for respiratory distress syndrome. Permanent closure of the ductus arteriosus occurred in 21 (58%) infants and in this group the mean 24 hour plasma indomethacin concentration was 037 Ag/ml. Partial success was achieved in 6 (17%) infants (mean 24 hour indomethacin concentration 0-34 Ag/ml) but in 9 patients (mean 24 hour indomethacin concentration 0-29 ,ug/ml) there was no clinical change. Although the mean 24 hour indomethacin concentration was lower in the group with no clinical change, this was not statistically significant. Five of the 21 patients in whom there was permanent closure of the ductus required more than one dose of indomethacin. The possible effects of birthweight and age at indomethacin treatment were difficult to separate because of the high negative correlation between these two variables. The chance of closure was enhanced significantly if the patient had either a birthweight of at least 1 kg or the age at indomethacin treatment did not exceed 10 days, or both. Six hour but not 24 hour indomethacin concentrations were higher in patients with a high birthweight treated at an early age.Indomethacin has gained wide acceptance as a potent constrictor of the ductus arteriosus in preterm infants with the respiratory distress syndrome.'-3 While both oral and rectal administration of indomethacin have led to variable closure rates-6 the closure rates with intravenous administration seem to be consistently higher.3 There have been no published studies from the United Kingdom on the use of intravenous indomethacin in ductal closure or on plasma indomethacin concentrations related to therapeutic effect. We have therefore studied the effect of this drug on preterm neonates who were being ventilated for active lung disease. We also measured the drug concentrations and related these to clinical effect. Patients and methodsPreterm infants born in the West Yorkshire region who required ventilation for respiratory distress syndrome and were considered to have a haemodynamically patent ductus arteriosus were eligible for inclusion in the study. Twenty five of 38 infants were studied at one of two hospitals in Leeds; the remainder were at other hospitals in the region.We used the following clinical and radiological criteria for the diagnosis of patent ductus arteriosus:(1) A systolic murmur in the pulmonary area which did not have to extend throughout systole.(2) Bounding peripheral pulses. (3) Cardiomegaly and pulmonary plethora on chest radiograph.Criteria for exclusion from treatment with intravenous indomethacin were:(1) Tendency to excessive bleeding, a prolonged prothrombin time, prolonged partial thromboplastin time or a platelet count in peripheral blood of less than IOOx10'/l.

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Depolarizing stimuli increase the release of neurotransmitter met-enkephalin from rat striatal slices. Bay K8644, a calcium agonist, significantly enhances the submaximal release of this peptide. Several organic calcium antagonists, including nimodipine, nifedipine, nicardipine, gallopamil and flunarizine, are able to inhibit the potassium-evoked met-enkephalin release both in vitro and ex vivo. The data suggest that the release of this neuropeptide is modulated by calcium antagonist-sensitive calcium channels.