Diltiazem retards the metabolism of oral prednisone with effects on T- cell markers

The area under the time-plasma concentration curve (AUC) was measured for prednisolone (the major active metabolite of prednisone) after ingestion of 15 mg of prednisone (phase 1) and again after 3 d of oral diltiazem (180 mg/d) followed by the same dose of oral prednisone (phase 2) in eight normal adult patients. Diltiazem increased the prednisolone AUC by 21% (range 3- 38%), from 1297 ± 157 ng/h] mL to 1560 ± 169 ng/h/mL (p=0.001). This effect was associated with a greater decrease from baseline in CD3⁺ lymphocyte number at 4 h after prednisone ingestion (596 ± 175 vs. 516 ± 140, p=0.05), a larger percentage decrease of circulating CD3⁺ lymphocytes at 8 h (43 ± 19% vs. 53 ± 19%, p=0.04), and a decrease in the number of CD3⁺ CD8⁺ T cells at 4 h post-prednisone ingestion (279 ± 81 vs. 236 ± 51, p=0.04). Diltiazem retards prednisolone metabolism and when used chronically with prednisone could conceivably, in some patients, enhance its immunologic and other clinical effects. Potentiation of prednisone side-effects by diltiazem may be of special interest in pediatric patients, and possible diltiazem- prednisone interactions merit study in this population.