The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at physiological pH is obviously responsible for its better absorption and bioavailability when compared with ajmaline (Gilurytmal).

Prajmaline, the semisynthetic propyl derivative of ajmaline, shows a much better bioavailability when compared with the Rauvolfia alkaloid ajmaline. Early NMR and IR-studies, fluorescence spectroscopic investigations and extraction experiments combined with ion-pair chromatography proved the thesis of a tautomeric equilibrium between an aldehyde-amine and a quaternary carbinol-ammonium component. The aim of this study was to confirm this thesis by HPLC-separation and by structure-determination of both tautomeric compounds.

[A case of fatal poisoning with the anti-arrhythmia agents Katen and Neo-Gilurytmal]. / Letálny prípad intoxikácie antiarytmikami Katen a Neo-Gilurytmal.

The case is presented on 17-year-old student who ingested larger doses of tablets and capsules in privacy. She ingested antiarrhythmics Katen and Neo-Gilurytmal without clinical therapy by these drugs and without history of suicidal attempt. The imminent case of death was asphyxiation by aspiration of vomits from gastric contents after ingestion of excessive doses of drugs. The secondary findings as brain edema, petechiae under the serous membranes and congestion of the abdominal cavity, were relieved at autopsy. Noxae was identified by the postmortem toxicological analysis of blood, liver, kidney, gastric contents and intestinal contents. Mexiletine and prajmaline were analysed by the capillary gas chromatography with FID detection. Retention time of mexiletine was 6.66 minutes, prajmaline 15.15 minutes, respectively. Blood alcohol concentration was 0.21 mg.g-1. Concentration of prajmaline in gastric contents was 3.03 mg.g-1, mexiletine 0.11 mg.g-1, respectively.

[Cardiogenic shock and ventricular fibrillation induced by prajmalium and metoprolol poisoning]. / Kardiogén shock és kamrafibrilláció kialakulása prajmalin és metoprolol mérgezés következtében.

Prajmaline is not a relatively well known and frequently used antiarrhythmic belonging to Class IA group of antiarrhythmics, which was administered to a young male with metoprolol for the treatment of parasystole. The patient took in 120 mgs prajmaline and 600 mgs metoprolol during the day of the case, which leads to cardiogenic shock, ventricular tachycardia and ventricular fibrillation. The patient's parameters were normalized after successful resuscitation, temporary pacemaker and two days long Dopamin therapy. Therapy was not regarded to be necessary for a few ventricular premature beats detected during a week observation period. The patient is without complaints now, and significant ventricular arrhythmias, or malignant ventricular ectopy hasn't been proved with ECG tests and Holter monitoring for more than three months. Due to adverse effect profile of prajmaline, even at commonly used doses it should be administered carefully and other agents should probably be considered first before beginning long term treatment with prajmaline.

Pharmacokinetics and relative bioavailability of prajmalium bitartrate after single oral dosing.

Pharmacokinetics and relative bioavailability of the marketed prajmalium bitartrate tablet (Neo-Gilurytmal, CAS 2589-47-1) compared to an oral solution were investigated in an open, randomized, single-dose two-fold crossover study in 20 healthy male volunteers. One subject was identified to be a poor metabolizer. In the study population with normal metabolic status the two oral formulations proved to be bioequivalent with regard to the pharmacokinetic parameters Cmax, AUC(0-Tlast), AUC(0-infinity) and Ae(24h). tmax was prolonged after administration of the tablets. The relative bioavailability of prajmalium bitartrate from the tablet amounted to 112%. The poor metabolizer demonstrated in both oral formulations high plasma concentrations, increased AUCs and prolonged terminal half-lives as well as increased renal excretion of prajmalium bitartrate.