Time-dependent kinetics II: Diurnal oscillations in steady-state plasma ethosuximide levels in rhesus monkeys

✍ Scribed by Indravadan H. Patel; René H. Levy; Joan S. Lockard

• Publisher: John Wiley and Sons
• Year: 1977
• Tongue: English
• Weight: 447 KB
• Volume: 66
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600660512

✦ Synopsis

Morning steady-state (9 am) plasma levels were significantly higher than the corresponding evening (5 pm) plasma levels during a 3-week zero-order infusion of ethosuximide to six monkeys. These differences could not be explained by experimental variables such as GLC assay and infusion pump. Circadian periodicity in steady-state plasma levels was investigated in three monkeys over 4 months under controlled experimental conditions: blood sampling at 2-hr intervals for 26 hr, 1 day/week; fixed lighting, feeding, and noise schedules; and electroencephalogram monitoring. The plasma concentration-time curves showed two minima in the 12 noon-2 pm and 8 pm-12 midnight periods, and the later involved the largest percent change in plasma levels (4-8%). The plasma concentration-time data were subjected to cross-correlation analysis, which indicated a circadian rhythm in steady-state plasma levels with a period of 24-26 hr.