Relation between infusion rate of indomethacin and cerebral blood flow velocity

Background: Indomethacin is a very effective drug for patent ductus arteriosus (PDA). Decrease of cerebral blood flow, however, is an adverse effect of this drug. Differences in cerebral blood flow velocity (CBFV) with the different administration periods and the relation between CBFV and plasma drug level were investigated with the aim of establishing an administration protocol. Methods: The subjects were 14 neonates with PDA in the Neonatal Intensive Care Unit of Ehime Prefectural Central Hospital who received indomethacin. They were divided into two groups: 10 min drug infusion (n= 8) and 120 min drug infusion (n= 6). CBFV and blood concentration of indomethacin were measured. Results: CBFV in the10 min group was decreased significantly at 15 min and remained low until 120 min, but no significant change was seen in the 120 min group. The highest plasma levels in the 10 min group and 120 min group were 1257 ± 360 ng/mL and 819 ± 146 ng/mL, respectively. A comparison showed that the plasma level was significantly higher in the 10 min group, which had significantly lower CBFV. Changes in the plasma levels in the beta phase in the two groups were found to be almost the same. Ductus closure was confirmed in 13 of 14 neonates given indomethacin (10 min group, 7/8; 120 min group, 6/6). Conclusion: Slow administration of indomethacin >2 h is thought to be safer from the perspective of CBFV even though the clinical effect was unchanged.