Lockard J S, Levy R H, DuCharme L L, Congdon W C, Patel I H
Epilepsia. 1977 Jun;18(2):183-9. doi: 10.1111/j.1528-1157.1977.tb04466.x.
Four normal monkeys each equipped with an EEG plug and two indwelling catheters for drug infusion and sampling, respectively, were administered valproic acid (VPA) before and after a 12-hr light, 12-hr dark phase shift. Before day-night reversal, diurnal oscillations of VPA plasma levels under steady-state intravenous constant-rate infusions were 30-50%, with maximum concentrations during the dark phase of the cycle. After reversal, maximum VPA plasma concentrations tended to follow the dark phase shift. The correlation was not perfect, nor was the sleep cycle completely reversed since the animals slept less after the phase shift. Possible mechanisms of the diurnal plasma level fluctuations and the importance of oscillations of this magnitude to clinical drug regimens are discussed.
四只正常猴子，每只分别配备一个脑电图插头和两根分别用于药物输注和取样的留置导管，在12小时光照、12小时黑暗的昼夜相移前后给予丙戊酸（VPA）。在昼夜颠倒之前，在稳态静脉恒速输注下VPA血浆水平的昼夜振荡为30%-50%，在周期的黑暗阶段浓度最高。颠倒之后，VPA血浆最大浓度倾向于跟随昼夜相移。这种相关性并不完美，且睡眠周期也没有完全颠倒，因为动物在相移后睡眠减少。本文讨论了昼夜血浆水平波动的可能机制以及这种幅度振荡对临床药物治疗方案的重要性。
