Comparative bioavailability evaluation of two cyclosporine oral formulations in healthy Mexican volunteers.

BACKGROUND: The use of conventional cyclosporine (Sandimmune) requires great care, as this drug exhibits a narrow therapeutic index and wide interindividual variability in its pharmacokinetics. Recently, a new microemulsion formulation (Neoral) was developed. With this formulation, cyclosporine is absorbed at the small intestine without the presence of bile. Therefore, the objective of this study was to compare the bioavailability of cyclosporine after the administration of conventional and microemulsion formulations in healthy Mexican volunteers in order to approach the optimal dosage regimen of microemulsion in the Mexican population. METHODS: The trial was conducted using 23 healthy volunteers according to a randomized crossover design. Volunteers received one 7.5-mg/kg dose as each formulation, with a 1-week washout period between treatments. Blood samples of 0.5 mL were obtained according to the following schedule: 0, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 h after medication. RESULTS: These indicated that Cmax and AUC0-24 values were higher with the microemulsion than with the conventional formulation. CONCLUSIONS: The microemulsion had a better absorption profile than the conventional formulation, because plasma levels with the conventional formulation demonstrated oscillations rather than reflecting an erratic absorption. Lower doses of the microemulsion are required to obtain Cmax values similar to those obtained with conventional cyclosporine.

Acidos biliares sericos en la enfermedad hepatobiliar. / Serum biliary acids in hepatobiliary disease

Se determinaron los niveles sericos, de los acidos biliares colilglicina y sulfolitocolilglicina, por radioinmunoanalisis en varias enfermedades hepatobiliares como son: cirrosis secundaria a alcoholismo, cirrosis post-hepatitis, colestasis extrahepatica, absceso hepatico amibiano, hepatitis cronica activa y un grupo miscelaneo. La colilglicina se elevo principalmente, en aquellos padecimientos que cursaban con alteraciones hepatocelulares y obstruccion extrahepatica; los valores mas altos se observaron en pacientes con cirrosis hepatica secundaria a alcoholismo que cursaban con encefalopatia y en aquellos con obstruccion maligna. La sulfolitocolilglicina solo se incremento en la obstruccion extrahepatica por lo que se considera mas especifica y posiblemente de utilidad, para el diagnostico diferencial de colestasis. Se discuten las posibles causas que pueden intervenir en la elevacion de estos acidos biliares en los padecimientos hepatobiliares