Poley G E, Shively C A, Vesell E S
Clin Pharmacol Ther. 1978 Dec;24(6):726-32. doi: 10.1002/cpt1978246726.
After a single oral dose of aminopyrine (9 mg/kg), mean salivary aminopyrine half-lives (t 1/2s) and metabolic clearance rates in 12 normal male volunteers exhibited diurnal variations. Salivary aminopyrine t 1/2s were approximately 50% longer at 8 P.M. (2.1 +/- 0.7 hr) than at 8 A.M. (1.4 +/- 0.3 hr). Mean aminopyrine metabolic clearance rates decreased 20% from 8 A.M. (418.2 +/- 152.0 ml/min) to 8 P.M. (335.3 +/- 107.6 ml/min). There were large interindividual variations in the magnitude of these diurnal changes in aminopyrine t 1/2 and metabolic clearance rates. There were nonsignificant changes in mean aminopyrine apparent volumes of distribution (aVd) which increased only slightly from 53.1 +/- 20.6 L at 8 A.M. to 59.7 +/- 26.5 L at 8 P.M. There were diurnal variations in plasma 11-hydroxycorticosteroids (11-OHCS), mean values of which decreased 60% from 16.2 +/- 4.2 microgram/100 ml at 8 A.M. to 6.5 +/- 1.9 microgram/100 ml at 8 P.M. Sleeplessness for 24 or 48 hr under the conditions of this experiment failed to affect diurnal rhythms in aminopyrine metabolism or plasma 11-OHCS concentrations.
12名正常男性志愿者单次口服氨基比林（9毫克/千克）后，唾液中氨基比林的平均半衰期（t1/2s）和代谢清除率呈现出昼夜变化。唾液中氨基比林的t1/2s在晚上8点（2.1±0.7小时）比早上8点（1.4±0.3小时）长约50%。氨基比林的平均代谢清除率从早上8点（418.2±152.0毫升/分钟）到晚上8点（335.3±107.6毫升/分钟）下降了20%。这些氨基比林t1/2和代谢清除率的昼夜变化幅度存在很大的个体差异。氨基比林的平均表观分布容积（aVd）变化不显著，仅从早上8点的53.1±20.6升略微增加到晚上8点的59.7±26.5升。血浆11-羟基皮质类固醇（11-OHCS）存在昼夜变化，其平均值从早上8点的16.2±4.2微克/100毫升下降60%至晚上8点的6.5±1.9微克/100毫升。在本实验条件下连续24或48小时失眠并未影响氨基比林代谢或血浆11-OHCS浓度的昼夜节律。
