title: Ketamine kinetics in unmedicated and diazepam-premedicated subjects.
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.
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000758:Anesthesia; D003975:Diazepam / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D006801:Humans; D007275:Injections, Intravenous; D007649:Ketamine / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011897:Random Allocation; D012890:Sleep / Q000187:drug effects
chemical_list: D007649:Ketamine; D003975:Diazepam