317 PHENYTOIN KINETICS IN NEWBORNS

Abstract

To determine the relative contribution of age and absorption on phenytoin (PHT) kinetics in full-term newborns, we measured PHT apparent half-life (t_50%) 15 times in 9 infants aged 2 to 36 days. PHT was given i.v. 9 times and p.o. 6 times. The PHT t_50% ranged from 140 hours In a 2 day old to 3.78 hours in a 36 day old. Whereas the t_50% correlated directly with initial concentration (C_i) in the 8 patients ≥9 days old (r=0.755, p<.05), there was no correlation in 7 younger patients. T_50% varied inversely with age, averaging 84.7 hr (SD 42.6) in patients less than 8 days old and 14.7 hr (SD 7.74) in older patients (t=4.59, p<.01). Controlling for the effect of C_i, the average t_50% was still reduced by more than 3 times in the older group (84.7 vs 25.5 hr, p<0.02). Preliminary study of PHT absorption suggests that the reduction of PHT levels seen in infants more than 1 week old is even greater than predicted by this 3-fold increase in PHT eliminatory capacity and supports the notion that PHT bioavailability is significantly reduced in infants.

Thus, the relation between C_i and t_50% of PHT changes rapidly during the first month of life, a change which must be considered when studying PHT administration and absorption in newborns. For an individual newborn these kinetic changes are unpredictable and repeated PHT measurements are essential.

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