PICN (0.1 mg/kg/dose, q24H) initiated <24H from birth promotes closure of PDA in preterm infants with BW between 600-1250g and GA between 23-29wks (J Pediatr 1996; 128:631-7). Additional analysis of this data revealed that the mean GA(wks) and BW(g) of non-responders were significantly less than that of responders, 25.3±1.6 vs 26.7±1.5 and 794±174 vs 947±207, and that the mean ICN serum level obtained 24H post-1st dose was less, 0.22±0.66 vs 0.27±0.11 (mcg/ml), respectively (Ped Res 1996; 39:203A). A previous study noted that ductal closure was successful when the 24H post-1st dose serum ICN level was >0.25mcg/ml (NEJM 1981; 305:67-72). These data suggest that smaller, more premature infants have different ICN pharmacokinetics and will require a different dosing regimen to attain effective 24H post-1st dose serum ICN levels to promote ductal closure. The purpose of this study was to assess ICN pharmacokinetics in infants with BW<800g and GA<26wks and determine the dose needed to achieve a 24H 1st-dose level >0.25mcg/ml. In this study, 6 premature infants (BW: 600-800g, GA: 23-26wks) received PICN (0.15mg/kg) <24H following birth with subsequent doses (0.1mg/kg/dose, q24H) initiated 48H after the 1st dose. Serum ICN levels were obtained 2, 12, 24, 36 and 48H after the initial dose and prior to subsequent doses.

Results are summarized in the table shown below. These data suggest that an initial dose of PICN at 0.2mg/kg would be necessary to attain a 24H post-1st dose serum ICN level of >0.25mcg/ml in infants with BW<800g and GA<26 wks. Furthermore, because of the estimated prolonged half-life, further dosing may be unnecessary in this population.

Table 1 No caption available.
Full size table