FORMULATION OF DILTIAZEM AFFECTS CYCLOSPORINE-SPARING ACTIVITY

Objective: To consider the effect of changing from a conventional rele ase formulation of diltiazem to the controlled diffusion diltiazem for mulation on the cyclosporin-sparing effect in kidney transplant recipi ents. Methods: Seven stable renal transplant recipients were studied o n two separate occasions following at least 2 weeks stabilisation on e ither formulation. The order of administration of the two formulations was not randomised as all patients were already prescribed lower dosa ges of diltiazem before entering this phase of a larger study. The dos es of diltiazem used were 90 mg (conventional release diltiazem) taken twice daily and 180 mg controlled diffusion diltiazem taken in the mo rning. Results: Whilst there were no overall significant differences b etween the two formulations, the study demonstrated considerable inter patient variability when changing to the controlled diffusion formulat ion, particularly following the morning cyclosporin dose, with three p atients showing a reduced cyclosporin AUC (30-60%) and one an increase d cyclosporin AUC of 36%. Conclusion: A change in formulation of the c yclosporin-sparing agent may result in unpredictable alterations in cy closporin concentrations and resultant clinical sequelae.