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Does cholestyramine interfere with cyclosporine absorption? A prospective study in renal transplant patients.

Increased cardiovascular deaths have been reported in long-term survivors after renal transplantation. In the primary and secondary coronary prevention trials, reduction of elevated cholesterol has been demonstrated to decrease the incidence of cardiovascular events. The authors previously reported that only 33% of renal transplant patients achieved the National Cholesterol Education Program Expert Panel target values of total and low density lipoprotein cholesterol with niacin > or = 2 g/day or lovastatin 40 mg/day. Indeed, combination therapy with the bile acid sequestrant, cholestyramine appears to be a logical choice. Hence, the pharmacokinetics of cyclosporine were studies before (baseline, on day 1) and after starting cholestyramine 4 g/day, given as a single dose at noon (study repeated on day 4) in six nondiabetic renal transplant patients. Included were 1 woman and 5 men; their mean age (+/- SEM) was 45 +/- 6 years, and they were all > 1 year post transplantation. These patients were receiving cyclosporine, azathioprine, and prednisone based maintenance immunosuppression. Compared to day 1 (baseline period), the peak (644 +/- 142 ng/ml versus 625 +/- 168 ng/ml; ns) and trough (196 +/- 17 ng/ml versus 214 +/- 32 ng/ml; ns) cyclosporine levels and the time to peak (2 hr versus 2 hr) were not significantly different on day 4 (post cholestyramine period) of the study. Furthermore, the area under the curve (3721 +/- 586 ng/hour/ml versus 4143 +/- 778 ng/hour/ml; ns) was not significantly different. Our data suggest that cholestyramine 4 g, given once a day at noon, did not interfere with the absorption of oral cyclosporine. Hence, combination therapy with cholestyramine appears to be a reasonable choice in renal transplant patients with resistant hypercholesterolemia.