RESUMO
Linezolid is effective on many resistant organisms for the treatment of severe infections in burns. However, its pharmacokinetics was difficult to predict after major burns. The study aimed to describe the pharmacokinetic properties of linezolid administered intravenously at a dose of 10 mg/kg in severely burned rabbits in comparison to that in non-burns. Linezolid concentrations were quantitatively analyzed by high-performance liquid chromatography. The direct consequence of the physiological changes after burn injury was lower plasma linezolid concentrations. In addition, burn injury induced significantly altered pharmacokinetic parameters with higher inter-individual variability. The distribution volume and clearance rate were increased (2.88 vs. 1.92 L/kg, P > 0.05; 0.28 vs. 0.20 L/h/kg, P < 0.05), and the AUC0-∞ was significantly lower (37.99 vs. 51.47 mg/L h, P < 0.05). However, there were almost no changes in half-life and mean residence time. These results suggested that therapeutic drug monitoring and dosage individualization of linezolid in patients with severe burns were necessary.
Assuntos
Antibacterianos/farmacocinética , Queimaduras/metabolismo , Linezolida/farmacocinética , Administração Intravenosa/métodos , Animais , Área Sob a Curva , Queimaduras/microbiologia , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos/métodos , Meia-Vida , Taxa de Depuração Metabólica/efeitos dos fármacos , CoelhosRESUMO
Eleven new sesquiterpenoids, wenyujinins A-K (1-11), and a new monoterpenoid, wenyujinin L (12), were isolated from the rhizomes of Curcuma wenyujin. Their structures and relative configurations were elucidated using 1D and 2D NMR, X-ray crystallographic analysis, and HRESIMS data. The absolute configurations of 1, 2, 3, 4, 6, 8, 9, and 10 were determined by comparison of the experimental and calculated ECD spectra. The absolute configuration of 5 was determined from the ECD data of the [Rh2(OCOCF3)4] complex, whereas those of 7 and 12 were determined from the ECD spectra of the compounds alone. Compounds 7 and 7a strongly inhibited the induction of NO production by LPS, with IC50 values of 7.6 and 8.5 µM, respectively. Compounds 6 and 10 moderately inhibited NO production with IC50 values of 47.7 and 48.6 µM, respectively.
Assuntos
Curcuma/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Rizoma/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Animais , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Camundongos , Estrutura Molecular , Monoterpenos/química , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos/químicaRESUMO
On the basis of a sysmatic survey on literatures, this essay summarized the studies on chemical constituents and pharmacological activity of Curcuma wenyujin. According to statistics, the reports for chemical constituents of the plant were mainly concentrated between 2007 and 2010. So far, totally 82 compounds were reported, including 57 sesquiterpenoids, 6 diterpenoids, 6 monoterpenes and 10 other components. Particularly, 23 compounds were new. Studies on its pharmacological activity covered antitumor, anti-inflammatory, analgesic, hepatoprotective, antioxidant, antithrombotic and antithrombosis. This essay summarized its chemical constituents and pharmacological activity, in order to facilitate its studies, development and utilization.
