Age differences in trimethoprim pharmacokinetics: need for revised dosing in children?

The pharmacokinetics of trimethoprim was studied in children (nine girls 1.05 to 3.57 years old and nine girls 7.55 to 9.70 years old) with urinary tract infections and 12 healthy adults (27.07 to 44.62 years old) to investigate any age-related changes. Serum and urine concentrations were measured during 24 hours. The groups did not differ in the time or the height of the peak serum concentration. Thereafter the children had lower serum concentrations. They had a shorter elimination half-life (means: 1 to 3 years, 3.7 hours; 8 to 10 years, 5.4 hours; adults, 11.2 hours), because of the smaller volume of distribution (0.86 l/kg; 1.08 l/kg; 1.31 l/kg) and higher total clearance (2.8 ml/min/kg; 2.4 ml/min/kg; 1.4 ml/min/kg). The higher clearance in children was mainly nonrenal (metabolism). Calculation of the pharmacokinetic variables per unit of body surface area modified the age differences considerably. Compared with present dosage recommendations, trimethoprim in larger daily doses per kilogram of body weight for the children is suggested. The daily dose should be increased primarily by shortening the dose interval.