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Ketamine kinetics in unmedicated and diazepam‐premedicated subjects
Author(s) -
Domino Edward F,
Domino Steven E,
Smith Robert E,
Domino Laurence E,
Goulet J Richard,
Domino Kenneth E,
Zsigmond Elemer K
Publication year - 1984
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1984.235
Subject(s) - diazepam , ketamine , placebo , pharmacokinetics , volume of distribution , dosing , anesthesia , pharmacology , chemistry , medicine , alternative medicine , pathology
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 t½s were as follows: distribution (πt½) = 24.1 sec, redistribution (αt½) = 4.68 min, and elimination (βt½) = 2.17 hr. After diazepam‐ketamine dosing, t½s were: πt½ = 25.0 sec, αt½ = 6.37 min, and βt½ = 2.32 hr. Clinical Pharmacology and Therapeutics (1984) 36, 645–653; doi: 10.1038/clpt.1984.235