Swaisland A J
ICI Pharmaceuticals, Macclesfield, Cheshire, UK.
J Hum Hypertens. 1991 Dec;5 Suppl 2:69-71.
Co-administration of drugs with complementary action is a rational approach to the treatment of hypertension provided that the drugs are free of mutual pharmacokinetic interactions. The pharmacokinetics of single doses of lisinopril 10 mg alone, hydrochlorothiazide 12.5 mg alone, both drugs given concomitantly, and both given in a fixed combination tablet were studied in 24 healthy volunteers (including four women) using a randomized four-way crossover design with each treatment separated by 2 weeks. Timed blood and urine samples were collected for measurement of peak serum levels, area under the concentration vs time curve (AUC) and urinary recovery of lisinopril and hydrochlorothiazide. When given alone, peak serum levels of lisinopril (attained 6-8 hours post dose) were 44 ng/ml. Urinary recovery was 17.6% of the dose. Mean values after treatment with the combination tablet were only 2-6% lower, and co-administration with hydrochlorothiazide in free combination gave mean values 7% higher than the fixed-dose combination. Time to peak serum levels did not vary between treatments. Dosing with hydrochlorothiazide alone resulted in a mean peak serum concentration of 53 ng/ml, 2-6 hours post dose. The combination tablet resulted in a peak serum level and AUC for hydrochlorothiazide about 10% lower. The corresponding values for the free combination were only about 7% lower. The results indicate no clinically relevant pharmacokinetic interaction between the two components when administered in a single tablet.
如果药物之间不存在相互药代动力学相互作用，联合使用具有互补作用的药物是治疗高血压的一种合理方法。采用随机四交叉设计，每种治疗间隔2周，在24名健康志愿者（包括4名女性）中研究了单剂量10 mg赖诺普利、单剂量12.5 mg氢氯噻嗪、两种药物同时服用以及两种药物制成的固定复方片剂的药代动力学。定时采集血液和尿液样本，以测定赖诺普利和氢氯噻嗪的血清峰值水平、浓度-时间曲线下面积（AUC）以及尿回收率。单独给药时，赖诺普利的血清峰值水平（给药后6 - 8小时达到）为44 ng/ml。尿回收率为给药剂量的17.6%。服用复方片剂后的平均值仅低2 - 6%，与氢氯噻嗪自由联合给药时的平均值比固定剂量联合给药高7%。各治疗组之间血清峰值水平出现的时间没有差异。单独服用氢氯噻嗪给药后2 - 6小时的平均血清峰值浓度为53 ng/ml。复方片剂使氢氯噻嗪的血清峰值水平和AUC降低约10%。自由联合给药时的相应值仅低约7%。结果表明，两种成分制成单片给药时不存在临床相关的药代动力学相互作用。
