Summary
To ascertain whether the renal clearance of disopyramide (pKa = 8.36) is affected by urine pH, the disposition kinetics of disopyramide were compared during excretion of acidic and alkaline urine following both single dose intravenous (2 mg/kg) and oral (5mg/kg) administration to 4 healthy male volunteers. No significant difference was observed in the plasma concentration-time curve of disopyramide. The mean 72 hour recovery of disopyramide and its N-deisopropyl metabolite (MND) in urine was 55.1 and 20.3% of the dose respectively, with no apparent difference between the two routes of administration or pH of urine. Renal clearance of disopyramide was found to vary with time, which is partly the result of a concentration dependent change in plasma protein binding. The unbound fraction of drug in plasma varied from 0.32 to 0.72 between 0.4 to 4μg/ml concentration. However, time-dependent change in renal clearance of disopyramide persists even after correction for plasma protein binding.
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Ankier, S.I. and Kaye, C.M.: The influence of pH on the buccal absorption and renal excretion of disopyramide in man. British Journal of Clinical Pharmacology 3: 672–673 (1976).
Baines, M.W.; Davies, J.E.; Kellett, D.N. and Munt, P.L.: Some pharmacological effects of disopyramide and a metabolite. Journal of International Medical Research 4 (Suppl. 1): 5–7 (1976).
Borga, O.; Azarnoff, D.L.; Plym-Forshell, G. and Sjoqvist, F.: Plasma protein binding of tricyclic antidepressants in man. Biochemical Pharmacology 18: 2135–2144 (1969).
Coffey, J.J.: Effect of protein binding of drugs on areas under the plasma concentration-time curves. Journal of Pharmaceutical Sciences 61: 138–139 (1972).
Coffey, J.J.; Bullock, F.J. and Schoenemann, P.T.: Numerical solution of nonlinear pharmacokinetic equations: Effect of plasma protein binding on drug distribution and elimination. Journal of Pharmaceutical Sciences 60: 1623–1628 (1971).
Cunningham, J.L.; Shen, D.D.; Shudo, I. and Azarnofr, D.L.: The effect of non-linear pharmacokinetics on the systemic availability of disopyramide. Submitted to British Journal of Clinical Pharmacology.
Dean, R.R.: The pharmacology of Norpace. Angiology 26: 67–84 (1975).
Hinderling, P.H.; Bres, J. and Garrett, G.R.: Protein binding and erythrocyte partitioning of disopyramide and its monodealkylated metabolite. Journal of Pharmaceutical Sciences 63: 1684–1690 (1974).
Hinderling, P.H. and Garrett, E.R.: Pharmacokinetics of the antiarrhythmic disopyramide in healthy humans. Journal of Pharmacokinetics and Biopharmaceutics 4: 199–230 (1976).
Hulting, J. and Rosenhamer, G.: Anti-arrhythmic and haemodynamic effects of intravenous and oral disopyramide in patients with ventricular arrhythmia. Journal of International Medical Research 4 (Suppl. 1): 90–95 (1976).
Hutsell, T.C. and Stachelski, S.J.: The determination of disopyramide and its N-mono-dealkylated metabolite in blood, serum and urine. Journal of Chromatography 106: 151–158 (1975).
Jennings, G.; Jones, M.B.S.; Besterman, E.M.M.; Model, D.G.; Turner, P.P. and Kidner, P.H.: Oral disopyramide in prophylaxis of arrhythmias following myocardial infarction. Lancet 1: 51–54 (1976).
Jensen, G.; Sigurd, B. and Uhrenholt, A.: Circulatory effects of intravenous disopyramide in heart failure. Journal International Medical Research 4 (Suppl. 1): 42–45 (1976).
Jones, M.B.S.: The use of disopyramide in the treatment of arrhythmias in ambulatory patients. Journal of International Medical Research 4 (Suppl. 1): 86–89 (1976).
Jusko, W.J. and Levy, G.: Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin. Journal of Pharmaceutical Sciences: 765-772 (1970).
Karim, A.: The pharmacokinetics of Norpace. Angiology 26: 85–98 (1975).
Mizgala, H.F. and Huvelle, P.R.: Acute termination of cardiac arrhythmias with intravenous disopyramide. Journal of International Medical Research 4 (Suppl. 1): 82–85 (1976).
Morgan, P.H. and Mathison, I.W.: Arrhythmias and antiarrhythmic drugs: mechanism of action and structure-activity relationship II. Journal of Pharmaceutical Science 65: 635–648 (1976).
Rangno, R.E.: Warnica, W.: Ogilvie, R.I.: Kreeft, J. and Bridger, E.: Correlation of disopyramide pharmacokinetics with efficacy in ventricular tachyarrhythmia. Journal of International Medical Research 4 (Suppl. 1): 54–58 (1976).
Scatchard, G.: The attractions of protein for small molecules and ions. Annal of New York Academy of Sciences 51: 660–672 (1949).
Sutton, R.: Hemodynamics of intravenous disopyramide. Journal of International Medical Research 4 (Suppl. 1): 46–48 (1976).
Ward, J.W. and Kinghorn, G.R.: The pharmacokinetics of disopyramide following myocardial infarction with special reference to oral and intravenous dose regimens. Journal of International Medical Research 4 (Suppl. 1): 49–53 (1976).
Zaniel, N.; Jennings, G.; Jones, B.; Model, D.; Turner, P.; Besterman, M.A. and Kidner, P.H.: Disopyramide in the treatment and prevention of arrhythmias following myocardial infarction. Journal of International Medical Research 4 (Suppl. 1): 71–73 (1976).
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Supported by grants from Searle Research Laboratories and GM 15957 from the United States Public Health Service.
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Cunningham, J.L., Shen, D.D., Shudo, I. et al. The Effects of Urine pH and Plasma Protein Binding on the Renal Clearance of Disopyramide. Clin Pharmacokinet 2, 373–383 (1977). https://doi.org/10.2165/00003088-197702050-00004
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DOI: https://doi.org/10.2165/00003088-197702050-00004