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.
Imani
S
S
School of Medicine, University of California at San Diego, USA.
Jusko
W J
WJ
Steiner
R
R
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism*; D018655:Lymphocyte Count; D008875:Middle Aged; D011239:Prednisolone / Q000378:metabolism / Q000493:pharmacokinetics; D011241:Prednisone / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D013601:T-Lymphocytes
D002121:Calcium Channel Blockers; D007166:Immunosuppressive Agents; D003577:Cytochrome P-450 Enzyme System; D011239:Prednisolone; D004110:Diltiazem; D011241:Prednisone