ANTIHYPERTENSIVE EFFECT OF AMLODIPINE AND LACK OF INTERFERENCE WITH CYCLOSPORINE METABOLISM IN RENAL-TRANSPLANT RECIPIENTS

The catabolism of various calcium channel blockers through cytochrome P-450 is heterogeneous and may be modified by concomitant use of cyclo sporin A. In an open study we investigated the antihypertensive effect and clinical tolerance of the dihydropyridine amlodipine and its effe cts on cyclosporine kinetics in stable hypertensive renal transplant r ecipients not taking corticosteroids. Ten adult hypertensive patients grafted for 21.4+/-8.9 months and well stabilized with normal renal fu nction were included in the study. Renal artery stenosis was ruled out by normal Doppler echography. After 2 weeks of placebo, amlodipine wa s started at a daily dose of 5 mg. The dose was then adjusted to 10 mg if necessary. Blood and urine chemistries and whole-blood cyclosporin e trough levels were measured weekly. Cyclosporine kinetics were deter mined on a hourly basis before amlodipine administration and after 4 w eeks of treatment. Normal blood pressure was obtained with the use of 5 mg/d amlodipine in 7 patients and 10 mg/d in 3, diastolic blood pres sure decreasing from 98.7+/-3.8 to 81.3+/-9.1 mm Hg (P=.0007). Heart r ate slightly increased by 10% (P<.02). The drug was well tolerated, an d only minor ankle edema was found in 3 patients. Cyclosporine doses w ere not modified and cyclosporine levels remained unchanged throughout the study. Cyclosporine kinetic parameters were not significantly dif ferent at the beginning and end of the study. Bioequivalence was demon strated indicating that cyclosporine biotransformation was not altered by the concomitant administration of amlodipine. We conclude that aml odipine at the dosage of 5 to 10 mg/d is an efficient calcium channel blocker in hypertensive renal transplant recipients treated with cyclo sporine without corticosteroids. Moreover, amlodipine does not interfe re with cyclosporine diffusion and metabolism.