速尿制剂对利尿效果和效率的影响。
The influence of frusemide formulation on diuretic effect and efficiency.
作者信息
Wakelkamp M, Blechert A, Eriksson M, Gjellan K, Graffner C
机构信息
Division of Clinical Pharmacology, Department of Medical Laboratory Sciences and Technology, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
出版信息
Br J Clin Pharmacol. 1999 Sep;48(3):361-6. doi: 10.1046/j.1365-2125.1999.00015.x.
AIMS
Changes in drug delivery rate may result in clinically important changes in drug effects. For the loop diuretic frusemide, it would be desirable to develop controlled release preparations, that could maintain an effective urinary excretion rate over a prolonged period of time. The aim of this study was to investigate the influence of frusemide formulation on frusemide recovery, diuretic effect and efficiency.
METHODS
Twelve subjects were given 60 mg of four different frusemide controlled release formulations in a single-dose, double-blind, randomized 4-way cross-over design. The formulations were three study drugs with different extended dissolution rates (ER1Tab, ER2Tab and ER3Caps ) and one reference drug (LR). Urinary volume and contents of frusemide in urine were measured in samples collected over 24 h.
RESULTS
Substantial differences in frusemide recovery and diuretic efficiency were observed between LR and all other formulations. At 24 h, mean total frusemide recoveries of ER1Tab, ER2Tab and ER3Caps were 52%, 36% and 57% lower, respectively, compared with LR (P<0.01). Also at 24 h, mean total diuretic efficiency for ER1Tab, ER2Tab and ER3Caps was 83%, 31% and 135% higher, respectively, compared to LR. The rapid dissolution and absorption of LR resulted in a high diuretic response from 0 to 3 h after dosing. However, from 0 to 24 h, there were no differences in diuretic response between the formulations.
CONCLUSIONS
Controlled release formulations of frusemide with a low and extended rate of dissolution lead to a more prolonged absorption and subsequent diuresis, but still maintain a similar cumulative response, due to their higher diuretic efficiency.
目的
药物释放速率的变化可能导致药物效应出现具有临床意义的改变。对于袢利尿剂速尿而言，开发能够在较长时间内维持有效尿排泄率的控释制剂是很有必要的。本研究的目的是考察速尿制剂对速尿回收率、利尿效果及效能的影响。
方法
采用单剂量、双盲、随机四交叉设计，给12名受试者服用60mg的四种不同速尿控释制剂。这些制剂包括三种具有不同缓释速率的研究药物（ER1片、ER2片和ER3胶囊）和一种参比药物（LR）。在24小时内收集的尿液样本中测量尿量和尿中速尿的含量。
结果
观察到LR与所有其他制剂之间在速尿回收率和利尿效能方面存在显著差异。在24小时时，与LR相比，ER1片、ER2片和ER3胶囊的平均总速尿回收率分别降低了52%、36%和57%（P<0.01）。同样在24小时时，与LR相比，ER1片、ER2片和ER3胶囊的平均总利尿效能分别提高了83%、31%和135%。LR的快速溶解和吸收导致给药后0至3小时出现高利尿反应。然而，从0至24小时，各制剂之间的利尿反应没有差异。
结论
速尿控释制剂具有低且缓释的溶解速率，导致吸收和随后的利尿作用更持久，但由于其较高的利尿效能，仍维持相似的累积反应。
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