No abstract

Plasma ketamine concentrations after diazepam and placebo pretreatment were examined in a double-blind, randomized, cross-over study. Eight healthy male subjects received either diazepam or a 0.9% NaCl placebo before ketamine and received the alternate combination 5 to 24 days later. Ten minutes before ketamine dosing, diazepam, 0.3 mg/kg, or placebo in equal volume was injected intravenously at a rate not exceeding 5 mg/min. Ketamine, 2.2 mg/kg iv, was injected over 1 min. For the clinically relevant period for anesthesia (1 to 30 min), diazepam-ketamine treatment resulted in higher plasma levels at most time points, but diazepam pretreatment did not alter plasma levels of metabolite KI and pseudometabolite KII nor the 24-hr urinary excretion of ketamine, KI, and KII. Ketamine kinetics followed a three-term exponential decline under both treatment conditions. After placebo-ketamine dosing, plasma t 1/2s were as follows: distribution (pi t 1/2) = 24.1 sec, redistribution (alpha t 1/2) = 4.68 min, and elimination (beta t 1/2) = 2.17 hr. After diazepam-ketamine dosing, t 1/2s were: pi t 1/2 = 25.0 sec, alpha t 1/2 6.37 min, and beta t 1/2 = 2.32 hr.

Varying doses of d-amphetamine were given i.p. to young (28 day old), adult (approximately 90 day old), and geriatric rats (approximately 2 years old). 30 min after injection, rats were sacrificed and ACH extracted and assayed by pyrolysis gas-liquid chromatography. Total brain acetylcholine (ACh) levels were not significantly different among the control animals in all three groups, d-Amphetamine, however, decreased total levels of ACh in young and geriatric rats without changing levels in adult animals.The changes in young rats were dose-related. These results suggest an important difference in brain cholinergic mechanisms depending upon age. d-Amphetamine Acetylcholine Pyrolysis-gas chromatography Geriatric