Time-dependent kinetics II: Diurnal oscillations in steady-state plasma ethosuximide levels in rhesus monkeys.
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.
D000818:Animals; D002940:Circadian Rhythm; D004569:Electroencephalography; D004780:Environment, Controlled; D005013:Ethosuximide / Q000097:blood* / Q000494:pharmacology; D000882:Haplorhini; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D012890:Sleep / Q000187:drug effects; D013997:Time Factors
D005013:Ethosuximide