Hirate J, Watanabe J, Ozeki S
J Pharmacobiodyn. 1983 May;6(5):315-22. doi: 10.1248/bpb1978.6.315.
In order to clarify the change of disposition kinetics accompanied by growth, the whole-blood levels and whole-body autoradiography following intravenous administration of creatinine and urea, which are considered to pass through the water-filled pores of biological membranes easily, were investigated in 1-day-old, 1-week-old, 3-week-old and 8-week-old mice. For both creatinine and urea, the total body clearance was considerably lower in 1-day-old and 1-week-old mice than in more aged mice. Relatively lower renal clearance (i.e. rather incomplete renal function) in 1-day-old and 1-week-old mice was considered to be the major reason for this observation. Moreover, the lower metabolic clearance also seemed to be the cause in the case of urea, because the expiratory excretion of 14CO2 following the intravenous administration of 14C-urea was almost negligible in 1-day-old and 1-week-old mice in contrast to more aged (16-21%). The whole-body autoradiograms obtained following intravenous administration of 14C-creatinine indicated that creatinine was more rapidly transferred from blood to muscle in 1-day-old and 1-week-old mice, especially in 1-day-old mice, than in more aged mice. This might be caused by the difference in muscular blood flow rate or muscular cell membrane permeability to creatinine.
为了阐明伴随生长过程中处置动力学的变化,我们对1日龄、1周龄、3周龄和8周龄小鼠静脉注射肌酐和尿素后进行了全血水平和全身放射自显影研究,肌酐和尿素被认为很容易通过生物膜的水填充孔。对于肌酐和尿素,1日龄和1周龄小鼠的全身清除率明显低于年龄较大的小鼠。1日龄和1周龄小鼠相对较低的肾清除率(即肾功能相当不完善)被认为是这一观察结果的主要原因。此外,较低的代谢清除率似乎也是尿素这种情况的原因,因为与年龄较大的小鼠(16 - 21%)相比,1日龄和1周龄小鼠静脉注射14C - 尿素后14CO2的呼气排泄几乎可以忽略不计。静脉注射14C - 肌酐后获得的全身放射自显影片表明,与年龄较大的小鼠相比,1日龄和1周龄小鼠,尤其是1日龄小鼠,肌酐从血液向肌肉的转移更快。这可能是由于肌肉血流速度或肌肉细胞膜对肌酐的通透性存在差异所致。