title: Tolerability and kinetics of intravenous medifoxamine in healthy volunteers.
abstract: Medifoxamine is a new antidepressant drug which is in clinical use in France and is undergoing clinical investigation elsewhere. We have carried out a study of its tolerance by the intravenous route and have investigated its kinetic parameters by this route. Twelve healthy volunteers received single ascending intravenous doses of medifoxamine 5 to 10 mg. The subjects were observed for changes in haemodynamic and other vital signs. Serum samples were analyzed using a specific HPLC method. Medifoxamine was well tolerated by all volunteers. Its kinetics were described by a two-compartment open model with an elimination half-line 1.2 h, systemic clearance 1299 l/min, volume of distribution 1321 l and urinary excretion of parent drug less than 1% of the dose. One subject had high serum concentrations and low clearance when compared with the other subjects. This may have been due to genetic differences in drug metabolism, as this subject was found to be a poor metabolizer of debrisoquine.
authors.affiliation: Clinical Pharmacology, St. Bartholomew's Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Saleh
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.forename: T
authors.initials: T
authors.lastname: Edeki
authors.forename: P
authors.initials: P
authors.lastname: Turner
mesh_terms: D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007262:Infusions, Intravenous; D008657:Metabolic Clearance Rate / Q000502:physiology; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D005021:Ethylamines; D008996:Monoamine Oxidase Inhibitors; C034065:medifoxamine