Kondo Masatoshi, Kunikata Tetsuya, Okazaki Kaoru, Yasuda Saneyuki, Isobe Kenichi, Itoh Susumu
Division of Neonatal Unit, Ehime Prefectural Central Hospital, Ehime, Japan.
Pediatr Int. 2010 Aug;52(4):616-21. doi: 10.1111/j.1442-200X.2010.03126.x.
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.
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.
CBFV in the 10 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).
Slow administration of indomethacin > 2 h is thought to be safer from the perspective of CBFV even though the clinical effect was unchanged.
吲哚美辛是治疗动脉导管未闭（PDA）的一种非常有效的药物。然而，脑血流量减少是该药物的一种不良反应。为了制定给药方案，研究了不同给药期脑血流速度（CBFV）的差异以及CBFV与血浆药物水平之间的关系。
研究对象为14例在爱媛县中央医院新生儿重症监护病房接受吲哚美辛治疗的PDA新生儿。他们被分为两组：10分钟药物输注组（n = 8）和120分钟药物输注组（n = 6）。测量CBFV和吲哚美辛的血药浓度。
10分钟组在15分钟时CBFV显著降低，并持续至120分钟仍保持较低水平，但120分钟组未见显著变化。10分钟组和120分钟组的最高血浆水平分别为1257±360 ng/mL和819±146 ng/mL。比较显示，10分钟组的血浆水平显著较高，而其CBFV显著较低。发现两组β相血浆水平的变化几乎相同。14例接受吲哚美辛治疗的新生儿中有13例动脉导管闭合（10分钟组，7/8；120分钟组，6/6）。
从CBFV的角度来看，尽管临床效果不变，但吲哚美辛>2小时的缓慢给药被认为更安全。
