Elfner R, Achtert G, Hausleiter H J, Lentz A, Heene D L
Eur J Drug Metab Pharmacokinet. 1987 Jan-Mar;12(1):77-82. doi: 10.1007/BF03189865.
11 patients (9m, 2f, median age 59 years) with ventricular ectopic activity of at least Lown grade III received 20 mg N-Propyl-ajmaline-bitartrate (N-PAB) p.o. Plasma concentrations of N-PAB were determined with HPLC from blood samples within 26 hours after administration. An open two-compartment model was used. In 8 patients with normal function of the liver and the kidneys, the median clearance of N-PAB was 6.86 ml/min/kg and the median volume of distribution was 1.56 l/kg. Two patients had a clearly diminished clearance of 1.58 ml/min/kg without obvious impairment of liver or renal function. One patient with chronic glomerulonephritis (plasma creatinine 3.4 mg/dl) had a N-PAB clearance of 2.79 ml/min/kg. None of the Spearman rank correlation coefficients between the pharmacokinetic parameters of N-PAB with age, plasma albumin/globulin-quotient, plasma creatinine and cholin-esterase were significant. All calculated parameters were in the range determined in young subjects. It is concluded that physiological changes with age do not lead to significant changes of the pharmacokinetics of N-PAB. On the other hand in patients with increased levels of plasma creatinine a diminished clearance of N-PAB can be expected. It is also possible that patients without an obvious impairment of liver or renal function may have diminished N-PAB clearance.
11例(9例男性,2例女性,中位年龄59岁)至少有洛恩三级室性异位活动的患者口服20毫克酒石酸N - 丙基阿马林(N - PAB)。给药后26小时内从血样中用高效液相色谱法测定N - PAB的血浆浓度。采用开放二室模型。8例肝肾功能正常的患者中,N - PAB的中位清除率为6.86毫升/分钟/千克,中位分布容积为1.56升/千克。2例患者清除率明显降低至1.58毫升/分钟/千克,而肝肾功能无明显损害。1例慢性肾小球肾炎患者(血浆肌酐3.4毫克/分升)的N - PAB清除率为2.79毫升/分钟/千克。N - PAB的药代动力学参数与年龄、血浆白蛋白/球蛋白比值、血浆肌酐和胆碱酯酶之间的斯皮尔曼等级相关系数均无显著性。所有计算参数均在年轻受试者测定的范围内。结论是年龄引起的生理变化不会导致N - PAB药代动力学的显著变化。另一方面,血浆肌酐水平升高的患者可预期N - PAB清除率降低。肝肾功能无明显损害的患者也可能出现N - PAB清除率降低的情况。