RESUMO
As part of the development of a new series of antibacterial agents derived from coupling a beta-lactamic precursor with a fluoroquinolone and named cephalones, the pharmacokinetics of one derivate: CQ-M-EPCA in rats after intravenous, intragastric and intraduodenal routes, was carried out. After the IV injection of 20 mg/kg or 40 mg/kg of this cephalone, plasma concentrations at the time zero (Cp0) were 3.1 and 11.26 microg/ml, respectively. Plasma concentrations decreased rapidly to almost disappear in both instances. Forty-five minutes later, a surge in concentrations, in the 40 mg/kg group, with a maximal plasma concentration (Cpmax) of 2.97 microg/ml was observed. An elimination half-life (T1/2el) of 2.36 +/- 0.33 h. was calculated. The drug was undetected by the ninth hour. Intragastric administration of the drug resulted in Cpmax of 3.78 +/- 0.26 microg/ml with a time to reach Cpmax (Tmax) of 25 min and T1/2el = 3.22 h. Same variables after intraduodenal administration were Cpmax 4.71 microg/ml; Tmax 1h, and T1/2el 3.41 h. Outstandingly high bioavailabilities after intragastric and intraduodenal administration (169 and 246%, respectively), together with the shape of the concentration versus time profiles after IV administration suggest that the drug undergoes a complex redistribution phenomenon, while showing high tissue diffusion with an apparent volume of distribution of 3.33 l/kg.
Assuntos
Antibacterianos/farmacocinética , Fluoroquinolonas/farmacocinética , Administração Oral , Animais , Antibacterianos/administração & dosagem , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Duodeno/metabolismo , Fluoroquinolonas/administração & dosagem , Meia-Vida , Injeções Intravenosas , Intubação Gastrointestinal , Masculino , Ratos , Ratos WistarRESUMO
UNLABELLED: The small intestine of the rat shows morphologic and enzymatic changes that are associated with the weaning and may be alternated by the early weaning, however, the morphometric criteria have been disregarded. MATERIAL AND METHODS: In this study, the effects of precocious weaning (15 days) and prolonged weaning (32 days), on the size and number of villi; and crypts of small intestine, were analyzed in rats from 16 to 70 days of age. RESULTS: Precocious weaning increased the size of villi, depth and number of crypts in the duodenum and jejunum, while the number of villi decreased. Pups nursed up to 32 days showed no alterations in the analyzed parameters. However, the ileum showed no alterations with the precocious weaning or prolonged. CONCLUSIONS: These data support the concept of an intrinsic biologic program as control of intestinal development while the change of diet seem to have a modifying role in duodenum and jejunum.