Ito K, Niida Y, Sato J, Owada E, Ito K, Umetsu M
Department of Pediatrics, Hokkaido Children's Hospital and Medical Center, Japan.
Acta Paediatr Jpn. 1994 Aug;36(4):387-91. doi: 10.1111/j.1442-200x.1994.tb03207.x.
The pharmacokinetics of mefenamic acid (MA), 2 mg/kg, were studied in 17 preterm infants with symptomatic patent ductus arteriosus. They were given this dosage orally at 24 h intervals. There were marked inter-individual differences in some of the pharmacokinetic parameters after the first dose; peak plasma concentration (Cmax) varied from 1.2 to 6.1 micrograms/mL with a mean of 3.8 micrograms/mL, time to reach Cmax (tmax) varied from 2 to 18 h with a mean of 7.7 h and plasma half-life (t1/2) varied from 3.8 to 43.6 h with a mean of 18.7 h. The group of infants (10/17) who had ductus closure after the first dose had significantly lower clearance (P < 0.01), longer t1/2 (P < 0.01) and higher 24 h plasma concentration (P < 0.001) compared to the group of infants (7/17) who had no ductus closure after the first dose. It appeared that the plasma concentration of MA had to be above 2.0 micrograms/mL and maintained at this concentration for at least 12 h for MA associated with ductus closure in preterm infants to take effect. In view of the inter-individual variation of plasma MA concentration and the effective plasma concentration, we suggest that measurement of the plasma concentration should be done 24 h after the first dose. This might be useful for safe and effective therapy for infants with ductus closure failure after the first dose.
对17例有症状的动脉导管未闭早产儿进行了2mg/kg甲芬那酸（MA）的药代动力学研究。他们每隔24小时口服该剂量。首剂后部分药代动力学参数存在明显的个体差异；血浆峰浓度（Cmax）为1.2至6.1微克/毫升，平均为3.8微克/毫升；达峰时间（tmax）为2至18小时，平均为7.7小时；血浆半衰期（t1/2）为3.8至43.6小时，平均为18.7小时。与首剂后动脉导管未闭的婴儿组（7/17）相比，首剂后动脉导管闭合的婴儿组（10/17）的清除率显著降低（P<0.01），t1/2更长（P<0.01），24小时血浆浓度更高（P<0.001）。似乎MA的血浆浓度必须高于2.0微克/毫升并维持该浓度至少12小时，MA才会对早产儿动脉导管闭合起作用。鉴于血浆MA浓度的个体差异和有效血浆浓度，我们建议在首剂后24小时测定血浆浓度。这可能有助于对首剂后动脉导管闭合失败的婴儿进行安全有效的治疗。
