Phenytoin and phenobarbital stable isotope studies in neonates.

A pharmacokinetic study of phenytoin and phenobarbital with nonradioactive isotopes was performed in nine neonates in an intensive care unit setting. A single-pulse dose of either labeled phenobarbital (1,3-(15)N, 2-(13)C) or labeled phenytoin (2-(13)C, 1, 3-(15)N) was administered to neonates who manifested gestation between 25 and 40 weeks and were receiving maintenance medication. Blood samples were collected at fixed intervals, and with a computerized gas chromatography mass spectrometry system, plasma concentrations of the labeled and unlabeled drug in relation to time administered were obtained. According to the calculations obtained from labeled analogue, several kinetic characteristics related to drug absorption, clearance, and elimination were determined. The use of a nonradioactive labeled isotope overcomes the limitations of conventional pharmacokinetic methodology and can be specifically useful in neonates and infants in whom volumes of distribution are rapidly changing and steady state is not achieved.