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.

Monounsaturated fatty acid (avocado) rich diet for mild hypercholesterolemia.

To assess the effect of a high monounsaturated fatty acids (MFA) diet on serum lipids, 30 healthy adult normolipidemic volunteers and 37 adult patients with mild hypercholesterolemia (5.4-9.3 mmol/l), 15 of them also with hypertriglyceridemia (2.3-4.8 mmol/l), were studied. Fifteen healthy and 30 hypercholesterolemic subjects (15 of them with associated type 2 diabetes mellitus) received an avocado enriched diet (2000 Kcal, lipids 53% MFA 49 g saturated/unsaturated ratio 0.54), and seven non-diabetic hypercholesterolemic individuals received an isocaloric control diet (MFA 34 g, saturated/unsaturated ratio 0.7). Serum total cholesterol, LDL-cholesterol, HDL-cholesterol and triglyceride concentrations were measured before and after a 7-day diet period. In healthy individuals a 16% decrease of serum total cholesterol level followed the high MFA diet, while it rose after the control diet (p < 0.001 between diets). In hypercholesterolemic subjects a significant (p < 0.01) decrease of serum total cholesterol (17%), LDL-cholesterol (22%) and triglycerides (22%), and increase of HDL-cholesterol (11%) levels occurred with the avocado diet, while no significant changes were noticed with the control diet. High lipid, high MFA-avocado enriched diet can improve lipid profile in healthy and especially in mild hypercholesterolemic patients, even if hypertriglyceridemia (combined hyperlipidemia) is present.