Smith C L, Hampton E M, Pederson J A, Pennington L R, Bourne D W
Department of Pharmacy Practice and Administration, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855-0789.
Pharmacotherapy. 1994 Jul-Aug;14(4):471-81.
The effect of the diltiazem-cyclosporine interaction on cyclosporine pharmacokinetics, pharmacodynamics, and pharmacoeconomics was studied in 10 recipients of renal allografts. Each subject was studied while receiving diltiazem 60 mg twice/day and while not taking the drug. After achieving steady-state conditions, cyclosporine and metabolite concentrations were determined in whole blood from samples drawn after the morning cyclosporine dose. After pharmacokinetic analysis, all patients were followed for 6 months during treatment with cyclosporine plus diltiazem or cyclosporine alone. Cyclosporine blood clearance decreased significantly after treatment with diltiazem (18.0-11.0 ml/min.kg; p = 0.008). The apparent volume of cyclosporine distribution also decreased significantly (4.26-2.62 L/kg; p < 0.05). After 6 months, diltiazem had no effect on renal function indexes, and no apparent effect on immunosuppression. Alterations in cyclosporine clearance and apparent volume of distribution secondary to diltiazem result in dosage reduction and potential cost savings in transplant pharmacotherapy. The mean decrease in cyclosporine dosage requirements would produce a cost saving of $1520 or 28% per patient per year.
在10例同种异体肾移植受者中研究了地尔硫䓬 - 环孢素相互作用对环孢素药代动力学、药效学和药物经济学的影响。每位受试者在接受每日两次60毫克地尔硫䓬治疗时以及未服用该药物时均接受研究。在达到稳态条件后，于早晨服用环孢素剂量后采集的全血样本中测定环孢素和代谢物浓度。经过药代动力学分析后，所有患者在接受环孢素加地尔硫䓬或单独使用环孢素治疗期间随访6个月。用地尔硫䓬治疗后，环孢素的血液清除率显著降低（18.0 - 11.0毫升/分钟·千克；p = 0.008）。环孢素的表观分布容积也显著降低（4.26 - 2.62升/千克；p < 0.05）。6个月后，地尔硫䓬对肾功能指标无影响，对免疫抑制也无明显影响。地尔硫䓬导致的环孢素清除率和表观分布容积的改变会使移植药物治疗中的剂量减少并可能节省成本。环孢素剂量需求的平均降低将为每位患者每年节省1520美元或28%的费用。
