caa a22 4500 469119128 CHVBK 20180323133133.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF02245480 doi (NATIONALLICENCE)springer-10.1007/BF02245480 Imipramine and 2-hydroxyimipramine: comparative cardiotoxicity and pharmacokinetics in swine [Elektronische Daten] [Bruce Pollock, James Perel] The hemodynamic, cardiographic, and initial pharmacokinetic characteristics of the de novo administration of the 2-hydroxymetabolite (2-OH-IMI) of imipramine (IMI), compared with its parent was studied in a swine preparation. Cardiac output, arterial pressure, and the continuous electrocardiogram were assessed after the intravenous administration of the drug or its metabolite. Plasma, sampled over 120 min and CSF sampled at 60 min were analyzed by reverse phase HPLC with spectroflurometric detection. Equilibrium dialyses were performed on plasma sampled at 60 min. 2-OH-IMI, in doses of 5-6 mg/kg, compared to dosages of IMI up to 8.5 mg/kg, produced a significantly greater incidence of life-threatening arrhythmias, and caused profound and significant decreases in blood pressure and cardiac output. 2-OH-IMI had a smaller volume of distribution (Vd) and shorter half-life. CNS penetration, as estimated by CSF/plasma ratios, was significantly greater for 2-OH-IMI. These phenomena were partly accounted for by significantly less protein binding for the hydroxymetabolite. It is concluded that 2-OH-IMI has increased penetrance into the CNS despite a smaller Vd and that it is significantly more cardiotoxic than its parent. Springer-Verlag, 1992 Antidepressive agents, tricyclic nationallicence Imipramine nationallicence Hydroxylation nationallicence Heart nationallicence Pharmacokinetics nationallicence Swine nationallicence Pollock Bruce Clinical Pharmacology Program, Departments of Psychiatry and Pharmacology, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA aut Perel James Clinical Pharmacology Program, Departments of Psychiatry and Pharmacology, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA aut Psychopharmacology Springer-Verlag 109/1-2(1992-10-01), 57-62 0033-3158 109:1-2<57 1992 109 213 https://doi.org/10.1007/BF02245480 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245480 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pollock Bruce Clinical Pharmacology Program, Departments of Psychiatry and Pharmacology, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Perel James Clinical Pharmacology Program, Departments of Psychiatry and Pharmacology, University of Pittsburgh, School of Medicine, Western Psychiatric Institute and Clinic, 3811 O'Hara Street, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 109/1-2(1992-10-01), 57-62 0033-3158 109:1-2<57 1992 109 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer