Asunto(s)
Asteraceae/química , Glicósidos/química , Fenoles/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Asteraceae/metabolismo , Glicosilación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Hojas de la PlantaRESUMEN
The aim of this study was to use the pharmacokinetic information of avicularin in rats to project a dose for humans using allometric scaling. A highly sensitive and specific bioanalytical assay to determine avicularin concentrations in the plasma was developed and validated for UPLC-MS/MS. The plasma protein binding of avicularin in rat plasma determined by the ultrafiltration method was 64%. The pharmacokinetics of avicularin in nine rats was studied following an intravenous bolus administration of 1 mg/kg and was found to be best described by a two-compartment model using a nonlinear mixed effects modeling approach. The pharmacokinetic parameters were allometrically scaled by body weight and centered to the median rat weight of 0.23 kg, with the power coefficient fixed at 0.75 for clearance and 1 for volume parameters. Avicularin was rapidly eliminated from the systemic circulation within 1 h post-dose, and the avicularin pharmacokinetic was linear up to 5 mg/kg based on exposure comparison to literature data for a 5-mg/kg single dose in rats. Using allometric scaling and Monte Carlo simulation approaches, the rat doses of 1 and 5 mg/kg correspond to the human equivalent doses of 30 and 150 mg, respectively, to achieve comparable plasma avicularin concentrations in humans.
Asunto(s)
Bidens/química , Flavonoides/farmacocinética , Extractos Vegetales/farmacocinética , Animales , Relación Dosis-Respuesta a Droga , Flavonoides/administración & dosificación , Flavonoides/sangre , Humanos , Inyecciones Intravenosas , Masculino , Modelos Biológicos , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Ratas Wistar , Espectrometría de Masas en TándemRESUMEN
Ocular toxoplasmosis may result in uveitis in the posterior segment of the eye, leading to severe visual complications. Clindamycin-loaded poly(lactide-co-glycolide) (PLGA) implants could be applied to treat the ocular toxoplasmosis. In this study, the pharmacokinetic profiles of the drug administrated by PLGA implants and by intravitreal injections in rabbits' eyes were evaluated. The implant released the drug for 6 weeks while the drug administrated by intravitreal injections remained in the vitreous cavity for 2 weeks. Compared to the injected drug, the implants containing clindamycin had higher values of area under the curve (AUC) (39.2 vs 716.7 ng week mL(-1)) and maximum vitreous concentration (Cmax) (8.7 vs 13.83 ng mL(-1)). The implants prolonged the delivery of clindamycin and increased the contact of the drug with the eyes' tissues. Moreover, the in vivo ocular biocompatibility of the clindamycin-loaded PLGA implants was evaluated regarding to the clinical examination of the eyes and the measurement of the intraocular pressure (IOP) during 6 weeks. The implantable devices caused no ocular inflammatory process and induced the increase of the IOP in the fourth week of the study. The IOP augmentation could be related to the maximum concentration of clindamycin released from the implants. In conclusion, the PLGA implants based on clindamycin may be a therapeutic alternative to treat ocular toxoplasmosis.
Asunto(s)
Clindamicina/análisis , Clindamicina/farmacocinética , Ensayo de Materiales/métodos , Espectrometría de Masas en Tándem/métodos , Cuerpo Vítreo/química , Animales , Cromatografía Liquida/métodos , Clindamicina/química , Evaluación Preclínica de Medicamentos/métodos , Implantes de Medicamentos , Ojo/química , Ojo/efectos de los fármacos , Inyecciones Intravítreas , Masculino , Conejos , Cuerpo Vítreo/efectos de los fármacosRESUMEN
Aberrant crypt foci (ACF) and colon rectal mucosal epithelial cell proliferation have been shown to be increased in patients with colon cancer and have been largely used for early detection of factors that influence colorectal carcinogenesis in rats. Fifty male Wistar rats were randomly divided into 5 groups. The groups G1 to G4 were given 4 injections of the carcinogen 1,2-dimethylhydrazine (DMH). The G2 group received Lychnophora ericoides (LE) extracts for 6 wk. The groups G3 and G4 received LE for 4 wk and 2 wk, respectively, at the postinitiation and initiation phases of colonic carcinogenesis. The group G5 was the control. Forty-two days after the first injections of DMH for the neoplasic induction, we observed a statistically significant decrease in the number of aberrant crypt foci (ACF) and an attenuation of the increase in cell proliferation induced by DMH in all the LE-treated groups. Thus, we concluded that Lychnophora ericoides extracts were effective against the development of cancer. These data suggest that LE has a protective influence on the process of colon carcinogenesis, suppressing both the initiation and the promotion of colonic carcinogenesis.