Pharmacokinetics of aditoprim in normal and febrile sheep

Aditoprim (2,4-diamino-5-[4-(dimethylamino) 3,5-dimethoxybenzyl] pyrimidine) is a recently developed inhibitor of bacterial dihydrofolate reductase with its structure closely resembling trimethoprim. It has an excellent in vitro bacteriostatic activity against both gram negative and gram positive bacteria and is considered to be a substantial improvement over trimethoprim to combat bacterial diseases in ruminants. Although the pharmacokinetics of aditoprim in normal healthy sheep has been reported, there have been no studies reported on the pharmacokinetics of this drug in the febrile state, the condition in which this antibiotic is primarily used. Many clinical infections are manifested by a rise in body temperature and as a result show an alteration in the disposition profiles. This change in disposition characteristics may significantly alter the clinical effectiveness of drugs. Therefore, the present study was undertaken to investigate the disposition profile of aditoprim in normal and febrile sheep.