Pharmacokinetics and metabolism of trimethoprim in neonatal and young pigs.
The pharmacokinetics and metabolism of trimethoprim (TMP) was studied in newborn, 1 and 8-week-old piglets after intravenous administration of 5 mg/kg. Kinetic parameters were calculated using a two-compartment open model. Steady-state volume of distribution increased from 0.78 L/kg at birth to 1.32 L/kg at 1 week, and 1.83 L/kg at 8 weeks due to changes in plasma protein binding and tissue accumulation. Elimination half-life decreased from 485 minutes at birth to 224 minutes at 1 week, and 120 minutes at 8 weeks leading to a rise in body clearance from 1.18 to 11.8 ml/min/kg during the same period. Urinary excretion data indicated that the increase in body clearance reflects maturational changes in both metabolic capacity and renal function. Metabolism was the main contributor to the elimination of TMP at all ages, although the major metabolic pathway, O-demethylation and subsequent conjugation, was only slightly developed at birth. The capacity to form conjugates with either glucuronic acid or sulphate appeared to be at least as high as the capacity for O-demethylation since more than 90% of the metabolites were excreted as conjugates in all groups.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001711:Biotransformation; D005260:Female; D005965:Glucuronates / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D013431:Sulfates / Q000378:metabolism; D013552:Swine; D014295:Trimethoprim / Q000378:metabolism* / Q000652:urine
D005965:Glucuronates; D013431:Sulfates; D014295:Trimethoprim