Laher M S, Mulkerrins E, Hosie J, Connell P A, Smith R P, Swaisland A J
James Connolly Memorial Hospital, Dublin, Eire, UK.
J Hum Hypertens. 1991 Dec;5 Suppl 2:77-84.
The pharmacokinetics of combined lisinopril and hydrochlorothiazide have been studied following single and multiple oral doses to 'young' (reference), elderly and renally impaired hypertensive patients. Tablets containing the fixed combination of lisinopril 20 mg and hydrochlorothiazide 12.5 mg were administered as a single dose followed by daily administration for 6-8 days. Serum concentration and haemodynamic measurements were made at intervals up to 48 hours after the first and last doses. The serum profiles of both drugs were comparable with observations from previous studies, showing higher concentrations in the elderly and in the renally impaired patients. Similar differences have been reported for such patient groups when the drugs were administered separately, indicating an absence of pharmacokinetic interaction. Both drugs accumulated by about 30% on multiple daily dosing. There were no differences between the patient groups in the extent of accumulation. The combination of lisinopril and hydrochlorothiazide produced the expected hypotensive response, minimum BP values being recorded 4 and 6 hours after treatment. The higher concentrations in the elderly and renally impaired patients were not associated with a greater reduction in BP. The pharmacokinetic behaviour of lisinopril and hydrochlorothiazide given together to elderly and renally impaired hypertensive patients suggests that a fixed dose combination is appropriate and that no changes to the dosage regimen additional to those used for the individual agents are necessary.
已对“年轻”（参照）、老年和肾功能受损的高血压患者单次及多次口服赖诺普利和氢氯噻嗪联合用药后的药代动力学进行了研究。给予含20毫克赖诺普利和12.5毫克氢氯噻嗪固定组合的片剂，单次给药后每日给药6 - 8天。在首次和末次给药后长达48小时的间隔时间进行血清浓度和血流动力学测量。两种药物的血清谱与先前研究的观察结果相当，显示老年患者和肾功能受损患者中的浓度更高。当分别给予这些药物时，此类患者群体也有类似差异的报道，表明不存在药代动力学相互作用。两种药物在每日多次给药时均蓄积约30%。患者群体之间在蓄积程度上无差异。赖诺普利和氢氯噻嗪联合用药产生了预期的降压反应，治疗后4小时和6小时记录到最低血压值。老年患者和肾功能受损患者中较高的浓度与更大程度的血压降低无关。赖诺普利和氢氯噻嗪联合给予老年和肾功能受损的高血压患者的药代动力学行为表明，固定剂量组合是合适的，且除了用于单一药物的给药方案外无需对给药方案进行其他改变。
