Difference in trimethoprim pharmacokinetics between children and adults

Area of Science:

• Pharmacology
• Pediatric Medicine
• Analytical Chemistry

Background:

• Trimethoprim (TMP) is an antibiotic commonly used for urinary tract infections.
• Understanding TMP pharmacokinetics in children is essential for optimizing treatment regimens.
• Previous pharmacokinetic data in pediatric populations is limited.

Purpose of the Study:

• To investigate the pharmacokinetics of trimethoprim (TMP) in children.
• To compare TMP elimination parameters between pediatric and adult subjects.
• To establish reference values for TMP half-life, volume of distribution, and plasma clearance in children.

Main Methods:

• A novel micromethod, adapted from a high-performance liquid chromatography (HPLC) assay, was employed.
• Five female children (1.08–9.71 years) with urinary tract infections received TMP suspension (6 mg/kg/day) for 10 days.
• Pharmacokinetic parameters were determined after the final dose, with three healthy adult males serving as controls.

Main Results:

• The half-life (t 1/2) of TMP was significantly shorter in children (3.0–5.5 h) compared to adults (9.3–13.6 h).
• The volume of distribution (Vd) was higher in children (0.7–1.1 L/kg) than in adults (0.5–0.9 L/kg).
• Plasma clearance (Clp) was notably greater in children (2.1–2.8 mL/min/kg) than in adults (0.4–1.2 mL/min/kg).

Conclusions:

• TMP exhibits a considerably shorter half-life in children than in adults.
• Pediatric patients demonstrate more rapid elimination and higher clearance of TMP.
• These findings highlight age-dependent pharmacokinetic differences crucial for pediatric TMP therapy.