Sato J, Kudo N, Owada E, Ito K, Niida Y, Umetsu M, Kikuta T, Ito K
Hokkaido College of Pharmacy, Japan.
Biol Pharm Bull. 1997 Apr;20(4):443-5. doi: 10.1248/bpb.20.443.
Urinary excretion of mefenamic acid (MA) and its two oxidative metabolites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivative), and their glucuronides was investigated in preterm infants undergoing MA therapy. MA was given orally at a dose of 2 mg/kg and the dose was repeated every 24 h a maximum of three times. Urine was collected for up to 5 d after the last dose, and MA and the metabolites were determined by a newly developed HPLC. The cumulative amounts of MA and the metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and were less than those reported in adults and children. Significant correlation was observed between the plasma half-life of MA and the cumulative amount of MA and the metabolites excreted in the urine. These results suggest that long plasma half-lives of MA observed in preterm infants are due mainly to low activity of drug metabolizing enzyme(s). In an infant who received the two regimens of MA therapy about 2 weeks apart, the plasma half-life of MA was shortened and the urinary excretion of the MA metabolites including their glucuronides was greatly increased during this period. It is suggested that the activities of both cytochrome P-450(s) and glucuronyltransferase(s) related to MA metabolism rapidly increased during the first month of the infant's life.
在接受甲芬那酸（MA）治疗的早产儿中，对甲芬那酸及其两种氧化代谢产物M-I（3'-羟甲基衍生物）和M-II（3'-羧基衍生物）及其葡糖醛酸苷的尿排泄情况进行了研究。以2mg/kg的剂量口服给予MA，每24小时重复给药一次，最多给药三次。在最后一剂给药后长达5天收集尿液，并通过新开发的高效液相色谱法测定MA及其代谢产物。尿液中排泄的MA及其代谢产物的累积量占给药总剂量的7%至46%，且低于成人和儿童的报告值。观察到MA的血浆半衰期与尿液中排泄的MA及其代谢产物的累积量之间存在显著相关性。这些结果表明，早产儿中观察到的MA较长的血浆半衰期主要是由于药物代谢酶活性较低。在一名间隔约2周接受两种MA治疗方案的婴儿中，在此期间MA的血浆半衰期缩短，包括其葡糖醛酸苷在内的MA代谢产物的尿排泄量大幅增加。提示与MA代谢相关的细胞色素P-450和葡糖醛酸转移酶的活性在婴儿出生后的第一个月内迅速增加。
