Hepatic biotransformation capacity in low-birth-weight infants as measured with the [15N]methacetin urine test: influences of gestational age, postnatal age, and intrauterine growth retardation.

The influences of the gestational age (range: 28-36 weeks) and the postnatal age (range: 6-100 days) on the biotransformation capacity of the liver were studied in 51 preterm appropriate-for-gestational-age infants and in 20 preterm small-for-gestational-age infants using the [15N]methacetin urine test. Methacetin is a test drug assessing a two-step pathway of biotransformation including monooxygenation and conjugation. After oral administration of 3 mg [15N]methacetin/kg body-weight, the cumulative 15N excretion in urine during the consecutive 9 h was measured and used as a marker of microsomal biotransformation capacity. In preterm appropriate-for-gestational-age infants, the biotransformation capacity increases with gestational age as well as with postnatal age, but the strongest correlation could be found between cumulative [15N] excretion and postmenstrual age. Intrauterine growth retardation results in lower biotransformation capacity (26.3 +/- 11.3 vs. 36.1 +/- 9.6% [15N] excretion, expressed as percentage of intake) and disturbed postnatal development of this hepatic function. The data indicate that normal intrauterine development is a prerequisite for normal postnatal development of the biotransformation capacity, which might have consequences for the metabolism and efficacy of certain drugs in small-for-gestational-age infants.