RESUMO
A simple high-performance liquid chromatographic method for the determination of dicloxacillin in plasma has been developed. The method only requires 0.5 ml of plasma, phosphate buffer solution (pH = 4.7), acidification with 0.5N hydrochloride acid and liquid extraction with dichloromethane. Posterior evaporation of organic under nitrogen steam and redissolution in mobile phase is carried out. The analysis was performed on a Spherisorb C18 (5 microm) column, using methanol -0.05 M phosphate buffer, pH = 4.7 (75:25; v/v) as mobile phase, with ultraviolet detection at 220 nm. Results showed that the assay is sensitive: 0.5 microg/ml. The response is linear in the range of 0.5 - 10 microg/ml. Maximum inter-day coefficient of variation was 12.4%. Mean extraction recovery obtained was 96.95%. Stability studies showed that the loss was not higher than 10%, samples are stable at room temperature for 6 h, at -20 Celsius for 2 months, processed samples were stable at least for 24 h and also after two freeze-thaw cycles. The method has been used to perform pharmacokinetic and bioequivalence studies in humans.
Assuntos
Antibacterianos/sangue , Cromatografia Líquida de Alta Pressão/métodos , Dicloxacilina/sangue , Antibacterianos/farmacocinética , Dicloxacilina/farmacocinética , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , Equivalência TerapêuticaRESUMO
Serum bactericidal titers against Staphylococcus aureus were measured in 63 children who were receiving mafcillin or methicillin intravenously, or dicloxacillin, penicillin, or cephalexin orally. The SBTs obtained following unit does of 25 mg/kg of dicloxacillin, 35 mg/kg of penicillin, or 25 mg/kg of cephalexin with probenecid were comparable to those seen following intravenous doses of 40 mg/kg nafcillin or methicillin. Twenty-two children with acute hematogenous osteomyelitis proven or presumed to be due to S. aureus were treated intravenously until point tenderness and fever had resolved, and then with oral therapy. The mean duration of intravenous therapy was 14 days. Oral doses were adjusted so that a peak SBT of greater than or equal to 1:16 and a trough SBT of greater than or equal to 1:2 were obtained in most children. No recurrences occurred. The SBT proved to be a practical means of assessing the adequacy of oral therapy in children with infections due to S. aureus.
Assuntos
Antibacterianos/sangue , Osteomielite/tratamento farmacológico , Administração Oral , Adolescente , Antibacterianos/administração & dosagem , Cefalexina/sangue , Criança , Pré-Escolar , Dicloxacilina/sangue , Relação Dose-Resposta a Droga , Avaliação de Medicamentos , Humanos , Lactente , Injeções Intravenosas , Meticilina/sangue , Nafcilina/sangue , Penicilina V/sangue , Probenecid/sangue , Ligação ProteicaRESUMO
A neonate treated initially with oxacillin intravenously for two weeks and who was receiving phenobarbital for a seizure disorder subsequently failed to achieve therapeutic levels of orally administered dicloxacillin, even when the dosage was as high as 175 mg/kg/day. Intestinal absorption was documented by high serum peak levels. The low trough levels correlated with a high urinary excretion rate. The possibillity that renal tubular transport of dichloxacillin was stimulated by administration of penicillin derivatives (and/or phenobarbital) is suggested, and the need for careful monitoring of serum levels of antibiotics in neonates is emphasized.