Patent ductus arteriosus
Springer Online Journal Archives 1860-2000
Summary We present pharmacokinetic data of prolonged, intra-arterial indomethacin treatment (i.e. induction plus maintenance dose) for symptomatic patent ductus arteriosus (sPDA) in 26 ventilated premature infants. sPDA was assessed by two-dimensional and pulsed Doppler echocardiography. Permanent ductal closure occurred in 20 (76%) infants. Plasma levels of indomethacin were 1.18±0.74; 1.8±1.0; 1.51±0.93 and 1.25±0.98 μg/ml (mean±SD) at 12, 24, 48 and 72 h after initial dose administration. All except one patient who responded with ductal closure, showed plasma levels above 0.25 μg/ml throughout the 3 day treatment period and no case of sPDA reopening was noted. Although target concentrations over time were not defined, the data indicate that the maintenance levels measured were within the therapeutic range. A negative correlation was found for plasma drug levels and postnatal age (r=0.52;P〈0.01). Volume of drug distribution was 0.23±0.18l/kg, total clearance 0.1±0.11 ml/min and elimination constant 0.06±0.05h−1 (mean±SD). The great variation in pharmacokinetic data reflects the heterogeneity of the population studied with respect to extracellular fluid space, cardiovascular status, serum protein and other parameters.
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