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Baquiloprim, a new antifolate antibacterial: in vitro activity and pharmacokinetic properties in cattle.
White, G; Daluge, S M; Sigel, C W; Ferone, R; Wilson, H R.
Afiliación
  • White G; Pitman-Moore Limited, Harefield, Uxbridge, Middlesex.
Res Vet Sci ; 54(3): 372-8, 1993 May.
Article en En | MEDLINE | ID: mdl-8337486
During examination of the half-lives in cattle of a series of 5-substituted diaminobenzyl-pyrimidines, it was found that replacement of the phenyl ring of trimethoprim (TMP) by bicyclic structures, particularly a quinolyl group, led to increases in half-life. The presence of a dimethylamino group on the quinolyl ring of the compound baquiloprim (BQP) conferred a half-life of about 10 hours. In contrast to TMP (half-life about one hour), BQP was well absorbed from the gastrointestinal tract in all ages of cattle, plasma concentrations reaching a plateau on the day after dosing followed by a slow decline. BQP showed the same high broad spectrum antibacterial activity as TMP, with marked synergy with sulphonamides. Its differential binding of the dihydrofolate reductases of Escherichia coli and rat liver predicted a margin of safety similar to that of TMP. The results of efficacy studies in mice in comparison with TMP showed that the longer half-life of BQP was associated with greater efficacy, and therapeutic properties superior to those of TMP in cattle were therefore predicted for BQP.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Bovinos / Antagonistas del Ácido Fólico / Antibacterianos Límite: Animals Idioma: En Revista: Res Vet Sci Año: 1993 Tipo del documento: Article Pais de publicación: Reino Unido
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pirimidinas / Bovinos / Antagonistas del Ácido Fólico / Antibacterianos Límite: Animals Idioma: En Revista: Res Vet Sci Año: 1993 Tipo del documento: Article Pais de publicación: Reino Unido