Tan A C, Jansen T L, Termond E F, Russel F G, Thien T, Kloppenborg P W, Benraad T J
Department of Experimental and Chemical Endocrinology, St. Radboud Hospital, University of Nijmegen, The Netherlands.
Eur J Clin Pharmacol. 1992;42(4):449-52. doi: 10.1007/BF00280134.
To study the influence of age on the kinetics of atrial natriuretic peptide (ANP) in man, human (99-126) ANP 2.0 micrograms.min-1 was infused IV for 60 min in 8 healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both baseline ANP values and the levels at the end of infusion were higher in the elderly subjects. The mean residence time of ANP in the two age groups was not significantly different, whereas total body clearance (CL) was markedly diminished in the elderly as compared to the young subjects (mean +/- SD 3.1 +/- 1.0 l.min-1 and 6.2 +/- 4.1 l.min-1, respectively). The apparent volume of distribution at steady state was lower in the elderly than in the young, but the difference was not significant (mean +/- SD 44 +/- 19 and 103 +/- 111, respectively. The decrease in CL largely explained the higher ANP levels found in the elderly subjects. The MRT and the plasma half-life of the terminal phase did not differ between the two groups. In the elderly but not in the young subjects the calculated endogenous creatinine clearance was closely correlated with the CL (r = 0.90, P less than 0.001), thereby emphasizing the importance of the kidney in the metabolic clearance of ANP in the elderly.
为研究年龄对人体心房利钠肽(ANP)动力学的影响,对8名健康青年(18至25岁)和9名健康老年(71至84岁)受试者静脉输注人(99 - 126)ANP 2.0微克·分钟⁻¹,持续60分钟。老年受试者的基线ANP值和输注结束时的水平均较高。两个年龄组中ANP的平均驻留时间无显著差异,而老年受试者的全身清除率(CL)与青年受试者相比明显降低(分别为平均±标准差3.1±1.0升·分钟⁻¹和6.2±4.1升·分钟⁻¹)。老年受试者稳态时的表观分布容积低于青年受试者,但差异不显著(分别为平均±标准差44±19和103±111)。CL的降低很大程度上解释了老年受试者中较高的ANP水平。两组之间MRT和终末相的血浆半衰期无差异。在老年受试者而非青年受试者中,计算得出的内生肌酐清除率与CL密切相关(r = 0.90,P < 0.001),从而强调了肾脏在老年受试者ANP代谢清除中的重要性。