Acute toxicity, antinociceptive, and anti-inflammatory activities of the orally administered crotamine in mice.

Crotamine is a polypeptide toxin isolated from rattlesnake venom. Although several studies have been developed identifying many biological effects of isolated crotamine, none of them evaluated its acute toxicity, antinociceptive, and anti-inflammatory activities through oral administration. All in vivo experiments from this study were performed in mice. The up-and-down procedure and hippocratic screening were carried out to evaluate possible pharmacological and toxic effects. Antinociceptive and anti-inflammatory activities of this toxin were evaluated using acetic acid-induced abdominal writhing, formalin-induced pain assays, croton oil-induced ear edema, and carrageenan-induced pleurisy. Crotamine did not cause lethality or signs of intoxication up to the maximum dose tested (10.88 mg/kg). The number of contortions was reduced significantly by 34, 57, and 74% at the oral doses of 0.08, 0.16, and 0.32 mg/kg, respectively. At the dose of 0.16 mg/kg, crotamine decreases pain time-reactivity at neurogenic phase by 45% and at inflammatory phase by 60%. Also, crotamine elicited antiedematogenic activity through the attenuation of the croton oil-induced ear edema by 77%. In the carrageenan-induced pleurisy, the leukocyte, neutrophil, and mononuclear cell migration to the lesion site were reduced by 52%, 46%, and 59%, respectively. Altogether, crotamine demonstrated in vivo antinociceptive and anti-inflammatory effect through acute oral administration, generating an anti-migratory mechanism of action at non-toxic doses.

Food-Effect on (-) - Hydroxycitric Acid Absorption After Oral Administration of Garcinia cambogia Extract Formulation: a Phase I, Randomized, Cross-Over Study.

Garcinia cambogia extract (GCE)/(-) - hydroxycitric acid (HCA) has been identified as a potential antiobesity agent. However, controversial clinical trial results have been published on its biological effect and poor pharmacokinetic (PK) information increases its dubious efficacy. The aim of this study was to determine the main PK parameters of GCE/HCA in healthy women, and to evaluate food effects on HCA absorption. Healthy women ages 21-41 years with body mass index (BMI; kg/m2) 20.29-25.82 participated in a phase I, open-label, randomized, single-dose, cross-over study. In the fasted- and fed-conditions subjects received 1500/750 mg of GCE/HCA under 8 h of fasting. In the fed-period was given a high calorie breakfast (~600 calories) after dosing. Plasma HCA concentrations were substantially reduced in fed-state. Peak plasma concentration (Cmax) and area under the curve of time-concentration (AUC0-10h) were 3-fold and 2-fold lower (p < 0.001, 0.01) in fed-condition, respectively. Higher volume of distribution (Vd/F) and clearance (Cl/F) were achieved in fed state, probably due to the lower fraction (F) of HCA absorbed induced by food effect. Large inter-individual variations were observed for the main pharmacokinetics parameters in both periods. These findings suggest that HCA might suffer an active absorption uptake and intense adsorption on food.