Changes in trimethoprim pharmacokinetics after the newborn period

The pharmacokinetics of trimethoprim administered orally or intravenously were investigated in six infants aged 1.7 months to 1.1 years. In these infants trimethoprim had a mean half life of 4.6 hours; this was comparable with the values found in young and school age children (3.8 and 5.4 hours respectively) and about a quarter of the half life in newborns. The volume of distribution (1.5 l/kg) was smaller than in newborns but larger than in young or school age children (0.9 and 1.1 l/kg respectively). The plasma clearance in these infants (3-3 ml/min/kg) was slightly larger than in newborns or in either group of older children (2.9 and 2.4 ml/min/kg respectively). Thus the most dramatic changes in trimethoprim pharmacokinetics seem to occur during the first two months of life. A reduced daily dose of trimethoprim is necessary during the first two months only. An increased daily dose, by addition of a third dose each day, is recommended from two months.