Pharmacokinetics of n-propyl-ajmaline-bitartrate in elderly patients with ventricular ectopic activity.

11 patients (9m, 2f, median age 59 years) with ventricular ectopic activity of at least Lown grade III received 20 mg N-Propyl-ajmaline-bitartrate (N-PAB) p.o. Plasma concentrations of N-PAB were determined with HPLC from blood samples within 26 hours after administration. An open two-compartment model was used. In 8 patients with normal function of the liver and the kidneys, the median clearance of N-PAB was 6.86 ml/min/kg and the median volume of distribution was 1.56 l/kg. Two patients had a clearly diminished clearance of 1.58 ml/min/kg without obvious impairment of liver or renal function. One patient with chronic glomerulonephritis (plasma creatinine 3.4 mg/dl) had a N-PAB clearance of 2.79 ml/min/kg. None of the Spearman rank correlation coefficients between the pharmacokinetic parameters of N-PAB with age, plasma albumin/globulin-quotient, plasma creatinine and cholin-esterase were significant. All calculated parameters were in the range determined in young subjects. It is concluded that physiological changes with age do not lead to significant changes of the pharmacokinetics of N-PAB. On the other hand in patients with increased levels of plasma creatinine a diminished clearance of N-PAB can be expected. It is also possible that patients without an obvious impairment of liver or renal function may have diminished N-PAB clearance.

[Localization of the binding site for quaternary derivatives of ajmaline in the Na channel of an excitable membrane]. / O lokalizatsii uchastka sviazyvaniia chetvertichnykh derivatov aimalina v Na-kanale vozbudimoi membrany.

The effects of external or internal application of quaternary derivatives of ajmaline and N-propyl ajmaline (NMA) to the frog nodes of Ranvier were studied by the voltage clamp method. It was established that external application of NMA is much less effective than that of the tertiary amine ajmaline or its quaternary analog N-ethyl ajmaline at comparable concentration. Even at a concentration of 1 mM NMA when applied externally caused only relatively insignificant tonic and use-dependent inhibition of sodium currents. In contrast, internal application of NMA (1 mM) through the cut ends of the fiber led to pronounced use-dependent inhibition of sodium currents. The conclusion is drawn that the binding site for NMA is located in the inner mouth of the Na channels which becomes available for the charged blocker only after opening of the activation gate.

[Pharmacokinetics and Antiarrhythmic effects of Prajmalium Bitartrate]. / Pharmakokinetik und antiarrhythmische Wirkung von Prajmaliumbitartrat.

8 patients with ventricular premature contractions were treated with prajmalium bitartrate (Neo-Gilurytmal) 20 mg q.i.d. The electrocardiograms were continuously monitored by a computerized arrhythmia monitoring system. For definition of the drug's pharmacokinetic properties plasma concentrations were determined. 7 patients showed a marked arrhythmia reduction. Mean ventricular premature contraction frequency was significantly reduced 6 h after onset of treatment, maximum arrhythmia suppression to 34% of control was observed after 24 h of treatment. The correlation of antiarrhythmic response and plasma concentrations was good. Mean plasma concentrations during steady state conditions were 218 ng/ml. Plasma half-life was determined 7.3 h. The lower limit of therapeutic plasma concentrations was between 43 and 145 ng/ml. A mean total clearance of 344 ml/min indicates a low hepatic extraction of prajmalium bitartrate. Moreover, the distribution volume of 204 l suggests a high tissue affinity of the drug.

[Pharmacokinetics and biotransformation of N-propylajmaline hydrogen tartrate in man]. / Pharmakokinetik und Biotransformation von N-Propyl-ajmalin-hydrogentartrat beim Menschen.

10 and 20 mg of N-Propyl-ajmalin-hydrogentartrate (N-PAB, Neo-Gilurytmal) were administered i.v. and orally respectively to healthy volunteers. In the study 14C-labelled N-PAB was used. The pharmacokinetics and the metabolic behaviour was examined. A fast and complete absorption of the compound could be observed. The bioavailability was 78%. The terminal plasma elimination half-life (beta-phase) was in the range of 4 to 6 hours. A total of 33% of the administered radioactivity was excreted via the kidney. 35 to 48% of the radioactivity found in urine was unchanged N-PAB. The excretion-kinetics of the three main metabolites as well as of the parent compound were determined. The possible presence of non-metabolizers is suggested.