Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases.

摘要: Objective. To determine the effect of chronic grapefruit juice administration on steady state blood concentrations cyclosporine and metabolites in patients with autoimmune diseases. Methods. 9 stabilized (range 0.7-6.7 mg/kg/day) were given either or water using a randomized crossover design. Whole samples collected before morning dose during 12 h interdose interval. Cyclosporine measured relatively specific assay (Emit®) total metabolite estimated nonspecific (polyclonal Abbott-TDx®). Results. Exposure to produced significant increases predose (p < 0.01) = 0.03) area under concentration-time curves 0.005, p 0.001, respectively). One patient developed neurological side effects associated 68.9 214% increase concentrations, respectively, coadministration. Conclusion. Grapefruit causes an both parent profiles, indicating alteration disposition metabolites. This interaction is potential clinical importance terms mechanism, effects, dosing.