Kiechel J R, Lavene D, Gurret M, Coustenoble J, Petrover M, Godin M, Fillastre J P
Nephrologie. 1980;1(2):73-81.
The pharmacokinetics of guanfacine (GF, antihypertensive agent with central action) were studied in five patients with renal insufficiency (CCr less than 30 ml/min) after oral administration of a single 4 mg dose. GF was rapidly absorbed, the peak plasma levels (13.28 +/- 1.58 ng/ml) being reached within two hours. The plasma level decreased with a bi-exponential pattern, with a t 1/2 of the beta phase of 24.4 +/- 3.2 h. The plasma clearance was 212 +/- 40 ml/min and the renal clearance 13.9 +/- 5.2 ml/min. The comparison of these results with those observed in hypertensive patients with a normal renal function demonstrates a slower elimination (t 1/2 beta in the reference group of 16.7 h) and a decrease of the total and renal clearances (445 +/- 29 ml/min and 144 +/- 6 ml/min respectively of the reference group) which directly correlated with the decrease of the CCr. The volume of distribution, however, does not seem to be modified. In 5 other patients under chronic dialysis treated with GF for several months, the cumulation was not more improvement than in the chronic renal insufficient group. The dialysis did not appear to interfere with the elimination kinetics of the drug.
对5例肾功能不全(肌酐清除率低于30 ml/min)患者口服单剂量4 mg胍法辛(GF,具有中枢作用的抗高血压药物)后的药代动力学进行了研究。GF吸收迅速,给药后两小时内达到血浆峰值水平(13.28±1.58 ng/ml)。血浆水平呈双指数模式下降,β相的半衰期为24.4±3.2小时。血浆清除率为212±40 ml/min,肾脏清除率为13.9±5.2 ml/min。将这些结果与肾功能正常的高血压患者的结果进行比较,发现清除较慢(参考组的β相半衰期为16.7小时),总清除率和肾脏清除率降低(参考组分别为445±29 ml/min和144±6 ml/min),这与肌酐清除率的降低直接相关。然而,分布容积似乎没有改变。在另外5例接受GF治疗数月的慢性透析患者中,药物累积情况并不比慢性肾功能不全组更好。透析似乎并未干扰药物的清除动力学。