Introduction of plasma indomethacin level monitoring and evaluation of an effective threshold level in very low birth weight infants with symptomatic patent ductus arteriosus

Abstract

First results are described of individually tailored indomethacin dose rates employing on-line drug level monitoring for pharmacologically induced ductal constriction in very low birth weight infants with symptomatic patent ductus arteriosus (sPDA). In addition prolonged indomethacin therapy was introduced. From our data it appears that the effective threshold indomethacin level for the induction of ductus constriction has to be about 1000 ng/ml 10 h postdosing, while ductus closure can be maintained with a dose rate that exceeds a plasma level of 500 ng/ml for at least 1 week. These maintenance levels were also effective in completely suppressing the urinary metabolite excretion rates of PGI2 and PGE2, which are potential mediators of ductal relaxation. On-line indomethacin level monitoring appears to be practically essential for prolonged indomethacin therapy to overcome the marked variation of indomethacin disposition in preterm infants with sPDA.