Linday L A, Drayer D E, Khan M A, Cicalese C, Reidenberg M M
Clin Pharmacol Ther. 1984 Apr;35(4):438-46. doi: 10.1038/clpt.1984.57.
To evaluate the effect of puberty on the net renal tubular secretion of digoxin, we measured the ratio of digoxin clearance to creatinine clearance in 23 patients aged 4 to 21 yr and correlated this ratio with both sexual maturity (Tanner stage) and chronologic age. All subjects were at steady-state levels for digoxin treatment; all had normal serum creatinine values for age as well as normal serum potassium levels. Mean ratio for immature children (n = 14, Tanner 1 through 3.5) was 1.45 +/- 0.66. Mean ratio for mature adolescents (n = 9, Tanner 4 through 5) was 0.95 +/- 0.28. The difference between the two groups was significant (P less than 0.05). When patients were regrouped by age using either 13 or 15 yr as a cutoff, the difference in ratios was no longer statistically significant. Based on 45 subjects (new and from our previous study) aged 2 mo to 80 yr, there was a significant decrease in the clearance ratio with increasing age, but when the 23 subjects aged 4 to 21 yr were analyzed separately, the correlation between ratio and age was not significant. It appears that the decrease in net renal tubular secretion of digoxin from childhood to adulthood correlates better with full sexual maturation at puberty (Tanner 4 through 5) than with chronologic age. This observation may represent a developmental change in pharmacokinetics with broader significance than for digoxin disposition alone.
为评估青春期对洋地黄净肾小管分泌的影响,我们测定了23例年龄在4至21岁患者的洋地黄清除率与肌酐清除率之比,并将该比值与性成熟度(坦纳分期)和实际年龄进行关联分析。所有受试者的洋地黄治疗均处于稳态水平;所有患者的血清肌酐值和血清钾水平均在其年龄对应的正常范围内。未成熟儿童(n = 14,坦纳1至3.5期)的平均比值为1.45±0.66。成熟青少年(n = 9,坦纳4至5期)的平均比值为0.95±0.28。两组间差异有统计学意义(P<0.05)。当以13岁或15岁为界按年龄对患者重新分组时,比值差异不再具有统计学意义。基于45例年龄在2个月至80岁的受试者(新纳入的及我们之前研究中的),清除率比值随年龄增长显著降低,但当单独分析23例年龄在4至21岁的受试者时,比值与年龄之间的相关性无统计学意义。从儿童期到成年期,洋地黄净肾小管分泌的减少似乎与青春期的完全性成熟(坦纳4至5期)的相关性比与实际年龄的相关性更好。这一观察结果可能代表了药代动力学的一种发育变化,其意义比仅针对洋地黄处置更为广泛。