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Pharmaceutisch weekblad

, Volume 1, Issue 1, pp 533–539 | Cite as

Disopyramide steady-state kinetiek bij patiënten met aritmieën

  • E. H. K. M. Gemmeke
  • M. J. S. Van Thiel
Voordrachten

Samenvatting

Enkele farmacokinetische parameters van disopyramide, in een steady-state situatie, werden bestudeerd bij acht patiënten met aritmieën. Er werd viermaal daags een capsule met 100 mg disopyramide base (Rythmodan®) toegediend.

Een gaschromatografische bepaling voor disopyramide in serum wordt beschreven.

De gemiddelde disopyramide serumspiegel bedroeg 2,74 ± 0,71 mg/l en was gelegen aan de ondergrens van het in de literatuur als therapeutisch beschouwde gebied van 2,5–5 mg/l. Een gemiddelde eliminatiehalfwaardetijd van 10,1 ± 3,6 uur werd berekend. Het gemiddeld fictief verdelingsvolume en de gemiddelde totale lichaamsklaring waren respectievelijk 1,37=0,29 l/kg en 0,101 ± 0,039 l. kg−1.h−1.

Het is gebleken dat er geen cumulatie van disopyramide optreedt bij chronisch gebruik van het farmacon.

Disopyramide steady-state kinetics in patients with arrhythmias

Abstract

Some pharmacokinetic parameters of disopyramide in a steady-state situation were studied in 8 patients with arrhythmias. Four times a day one capsule with 100 mg disopyramide base (Rythmodan®) was administered.

A gas-liquid chromatographic determination method for disopyramide in serum is described.

The mean disopyramide serum level amounted to 2.74±0.71 mg/l and was at the lower side of the therapeutic range of 2.5–5 mg/l, which is quoted in the literature. A mean elimination half-life of 10.1 ± 3.6 hours was calculated. The mean apparent volume of distribution and mean total body clearance were 1.37 ± 0.29 l/kg and 0.101 ± 0.039 l.kg−1.h−1, respectively.

There is no evidence for accumulation of disopyramide after chronic intake of the drug.

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Literatuur

  1. Baines, M. W., J. E. Davies enP. L. Munt (1976) Some pharmacological effects of disopyramide and a metabolite,J. Int. Med. Res. 4, Supplement (1) 5–7.PubMedGoogle Scholar
  2. Bryson, S. M., J. R.Lawrence en B.Whiting (1977) Disopyramide plasma kinetics and pharmacodynamics applied to the assessment of bioavailability,Brit. J. Clin. Pharmacol. 4, 633P.Google Scholar
  3. Deano, D., S. Swiryn, D. Best, R. Highley, D. Wu enK. Rosen (1978) Comparative efficacy of intravenous disopyramide and lidocaine in ventricular dysrhythmias,Am. J. Cardiol. 41, 416.CrossRefGoogle Scholar
  4. Duchateau, A. M. J. A., F. W. H. M. Merkus enF. Schobben (1975) Rapid gas chromatographic determination of disopyramide in serum using a nitrogen detector,J. Chromatog. 109, 432–435.CrossRefGoogle Scholar
  5. Duchateau, A. M. J. A., F. W. H. M. Merkus enR. Wilming (1977) Biofarmaceutische en farmacokinetische aspecten van disopyramide,Pharm. Weekblad 112, 145–154.Google Scholar
  6. Gee, J. P. (1978) Disopyramide,Drug Intell. Clin. Pharm. 12, 660–663.Google Scholar
  7. Heel, R. C., R. N. Brodgen, T. M. Speight enG. S. Avery (1978) Disopyramide: A review of its pharmacological properties and therapeutic use in treating cardiac arrhythmias,Drugs 15, 331–368.CrossRefPubMedGoogle Scholar
  8. Hillis, W. S., A. Tweddel, A. R. Lorimer enT. D. V. Lawrie (1976) Some aspects of the clinical pharmacology of intravenous disopyramide after myocardial infarction,J. Int. Med. Res. 4, Supplement (1), 74–77.PubMedGoogle Scholar
  9. Hinderling, P. H., J. Bres enE. R. Garrett (1974) Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite,J. Pharm. Sci. 63, 1684–1690.CrossRefPubMedGoogle Scholar
  10. Hinderling, P. H., enE. R. Garrett (1976) Pharmacokinetics of the anti-arrhythmic disopyramide in healthy humans,J. Pharmacokin. Biopharm. 4, 199–230.CrossRefGoogle Scholar
  11. Hulting, J., enG. Rosenhamer (1976) Anti-arrhythmic and haemodynamic effects of intravenous and oral disopyramide in patients with ventricular arrhythmia,J. Int. Med. Res. 4, Supplement (1) 90–95.PubMedGoogle Scholar
  12. Hutsell, T. C., enS. j. Stachelski (1975) Determination of disopyramide and its mono-N-dealkylated metabolite in blood serum and urine,J. Chromatog. 106, 151–158.CrossRefGoogle Scholar
  13. Jennings, G., M. B. S. Jones, E. M. M. Besterman, D. G. Model, P. P. Turner enP. H. Kidner (1976) Oral disopyramide in prophylaxis of arrhythmias following myocardial infarction,Lancet I, 51–54.CrossRefGoogle Scholar
  14. Jobst, Ch., enW. Enenkel (1978) Vergleichsstudie zwischen Disopyramid und Procainamid HCl per os in Fällen mit Extrasystolen,Herz/Kreisl. 10, 30–33.Google Scholar
  15. Karim, A. (1975) The pharmacokinetics of Norpace,Angiology 26, 85–98.PubMedGoogle Scholar
  16. Levy, G. (1974) Pharmacokinetic control and clinical interpretation of steady-state blood levels of drugs,Clin. Pharmacol. Therap. 16, 130–134.CrossRefGoogle Scholar
  17. Niarchos, A. P. (1976) Disopyramide: serum level and arrhythmia conversion,Am. Heart J. 93, 57–64.CrossRefGoogle Scholar
  18. Oshrain, C., M. Arif, J. C. Laidlaw, W. R. Cook enP. Willis (1976)A double-blind comparison of disopyramide phosphate and quinidine sulphate as anti-arrhythmic agents. Report from Scientific Exhibit, 40th Scientific Sessions, American Heart Association, Miami, Florida, Nov. 15–18.Google Scholar
  19. Pouleur, H., J. M. Chaudron enP. Reyns (1977) Effects of disopyramide and aprindine on arrhythmias after acute myocardial infarction,Europ. J. Cardiol. 5/5, 397–404.Google Scholar
  20. Rangno, R. E., W. Warnica, R. I. Ogilvie, J. Kreeft enE. Bridger (1976) Correlation of disopyramide pharmacokinetics with efficacy in ventricular tachyarrhythmia,J. Int. Med. Res. 4, Supplement (1) 54–58.PubMedGoogle Scholar
  21. Ranney, R. E., R. R. Dean, A. Karim enF. M. Radzialowski (1971) Disopyramide phosphate: pharmacokinetic and pharmacologic relationships of a new anti-arrhythmic agent,Arch. Int. Pharmacodyn. 191, 162–188.PubMedGoogle Scholar
  22. Rossum, J. M. Van (1976)Farmacokinetiek. Cursus Post Academisch Onderwijs,Knmp, Den Haag.Google Scholar
  23. Sandler, G. (1977) The use of disopyramide in resistant cardiac arrhythmias due to acute ischaemic heart disease,J. Int. Med. Res. 5, 369–373.CrossRefPubMedGoogle Scholar
  24. Smith, W. S., L. Vismara, R. B. Kalmansohn, R. V. Jutzy, W. R. Cook, D. M. Pugh, R. Berman, J. C. Laidlaw, C. Oshrain, L. S. Dreifus enT. Nisbet (1975) Clinical studies of Norpace. Parts i to xi.Angiology 26, (Suppl. 1) 124–153.PubMedGoogle Scholar
  25. Vismara, L. A., Z. Vera, R. R. Miller enD. T. Mason (1977) Efficacy of disopyramide phosphate in the treatment ofrefractory ventricular tachycardia,Am. J. Cardiol. 39, 1027–1034.CrossRefPubMedGoogle Scholar
  26. Ward, J. W., enG. R. Kinghorn (1976) The pharmacokinetics of disopyramide following myocardial infarction with special reference to oral and intravenous dose regimens,J. Int. Med. Res. 4, Supplement (1) 49–53.PubMedGoogle Scholar
  27. Whiting, B., enH. I. Elliott (1977) Disopyramide in renal impairment,Lancet II, 1363.CrossRefGoogle Scholar
  28. Zainal, N., J. W. Griffiths, D. J. S. Carmichael, E. M. M. Besterman, P. H. Kidner, A. D. Gillham enG. D. Summers (1977) Oral disopyramide for the prevention of arrythmias in patients with acute myocardial infarction admitted to open wards,Lancet II, 887–889.CrossRefGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1979

Authors and Affiliations

  • E. H. K. M. Gemmeke
    • 1
    • 2
  • M. J. S. Van Thiel
    • 3
  1. 1.Voordracht gehouden voor de Nederlandse Vereniging van ZiekenhuisapothekersThe Netherlands
  2. 2.Apotheek St. Jans GasthuisWeert
  3. 3.Apotheek DiaconessenhuisEindhoven

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