Jonkman J H, van Lier J J, van Heiningen P N, Lins R, Sennewald R, Högemann A
Pharma Bio-Research International, Zuidlaren, The Netherlands.
J Hum Hypertens. 1997 Sep;11 Suppl 2:S31-5.
The aim of this series of studies was to determine the potential for pharmacokinetic interaction between candesartan (administered orally as the prodrug candesartan cilexetil) and hydrochlorothiazide (HCTZ), nifedipine, glibenclamide, warfarin, digoxin or the components of an oral contraceptive formulation. All studies were performed in healthy volunteers using randomised, crossover or add-on study designs. Candesartan cilexetil was administered orally at doses of 8, 12 or 16 mg. The pharmacokinetic parameters were determined for comparator agents and candesartan following administration of each agent alone or in combination. There were no changes in the drug plasma concentrations of nifedipine, glibenclamide, digoxin or oral contraceptives when co-administered with candesartan cilexetil. Co-administration of candesartan cilexetil caused a slight but significant decrease in the AUC of HCTZ. However, the 90% confidence intervals (CI) for AUC ratios for HCTZ when co-administered with candesartan cilexetil were within the defined limits of bioequivalence. Candesartan cilexetil produced a 7% decrease in trough plasma warfarin concentration but this had no effect on prothrombin time. Co-administration of candesartan cilexetil with HCTZ produced a statistically significant increase in the bioavailability and Cmax values for candesartan (18% and 25%, respectively). However, this increase is not considered to be clinically relevant. No other co-administered drug (nifedipine, glibenclamide, digoxin, oral contraceptive) affected the pharmacokinetic parameters of candesartan. Candesartan cilexetil was well tolerated both alone and in combination with the other agents.
本系列研究的目的是确定坎地沙坦（以其前药坎地沙坦酯的形式口服给药）与氢氯噻嗪（HCTZ）、硝苯地平、格列本脲、华法林、地高辛或口服避孕药制剂的成分之间发生药代动力学相互作用的可能性。所有研究均在健康志愿者中采用随机、交叉或附加研究设计进行。坎地沙坦酯以8、12或16mg的剂量口服给药。在单独或联合给予每种药物后，测定了对照药物和坎地沙坦的药代动力学参数。当与坎地沙坦酯合用时，硝苯地平、格列本脲、地高辛或口服避孕药的血浆药物浓度没有变化。坎地沙坦酯与HCTZ合用时，HCTZ的AUC略有但显著降低。然而，坎地沙坦酯与HCTZ合用时HCTZ的AUC比值的90%置信区间（CI）在生物等效性的规定范围内。坎地沙坦酯使华法林的谷浓度降低了7%，但这对凝血酶原时间没有影响。坎地沙坦酯与HCTZ合用时，坎地沙坦的生物利用度和Cmax值有统计学意义的增加（分别为18%和25%）。然而，这种增加不被认为具有临床相关性。没有其他合用药物（硝苯地平、格列本脲、地高辛、口服避孕药）影响坎地沙坦的药代动力学参数。坎地沙坦酯单独使用或与其他药物合用时耐受性良好。
