URINARY-EXCRETION OF MEFENAMIC-ACID AND ITS METABOLITES INCLUDING THEIR ESTERGLUCURONIDES IN PRETERM INFANTS UNDERGOING MEFENAMIC-ACID THERAPY

Urinary excretion of mefenamic acid (MA) and its two oxidative metabol ites, M-I (3'-hydroxymethyl derivative) and M-II (3'-carboxyl derivati ve), and their glucuronides was investigated in preterm infants underg oing 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 mere de termined by a newly developed HPLC. The cumulative amounts of MA and t he metabolites excreted in the urine varied from 7 to 46% of the total dose administered, and mere less than those reported in adults and ch ildren. Significant correlation was observed between the plasma half-l ife 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 me tabolizing 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 glucu ronides 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 o f the infant's life.