Summary
The elimination of quinidine in humans is accomplished by a combination of renal excretion of the intact drug (15 to 40% of total clearance) and hepatic biotransformation to a variety of metabolites (60 to 85% of total clearance). Many of the metabolites appear to be pharmacologically active. Typical ranges for kinetic properties of quinidine in healthy persons are: apparent volume of distribution 2.0 to 3.5 litres/kg: elimination half-life 5 to 12 hours; clearance, 2.5 to 5.0ml/min/kg. Quinidine clearance is reduced in the elderly, in patients with cirrhosis, and in those with congestive heart failure.
Oral quinidine is available either as relatively rapidly absorbed conventional tablets (usually quinidine sulphate) or as a variety of slowly absorbed sustained release preparations. Absolute systemic availability generally is 70% or greater.
Quinidine is 70 to 95% bound to plasma protein, primarily to albumin but also to a number of other plasma constituents. Binding is reduced in patients with cirrhosis, partly because of hypoalbuminaemia, but is not influenced by renal insufficiency. Clinical interpretation of total serum or plasma quinidine concentrations must be altered in patients with reduced or increased binding, since it is the unbound fraction which is pharmacologically active.
Similar content being viewed by others
References
Achari, R.G.; Baldridge, J.L.; Koziol, T.R. and Yu, L.: Rapid determination of quinidine in human plasma by high-performance liquid chromatography. Journal of Chromatographic Science 16: 271–273 (1978).
Affrime, M. and Reidenberg, M.M.: The protein binding of some drugs in plasma from patients with alcoholic liver disease. European Journal of Clinical Pharmacology 8: 267–269 (1975).
Aviado, D.M. and Salem, H.: Drug action, reaction, and interaction. I. Quinidine for cardiac arrhythmias. Journal of Clinical Pharmacology 15: 477–485 (1975).
Balazs, T.; Herman, E. and Atkinson, J.: Comparison of effects of quinidine and di-hydroquinidine on canine heart. Journal of Pharmaceutical Sciences 67: 1355–1357 (1978).
Bellet, S.; Roman, L.R. and Boza, A.: Relation between serum quinidine levels and renal function. American Journal of Cardiology 27: 368–371 (1971).
Belpaire, F.M.; Bogaert, M.G. and Mussche, M.M.: Influence of acute renal failure on the protein binding of drugs in animals and in man. European Journal of Clinical Pharmacology 11: 27–32 (1977).
Bigger, J.T.: The quinidine-digoxin interaction: What do we know about it?. New England Journal of Medicine 301: 181–779 (1979).
Bolme, P. and Otto, U.: Dose-dependence of the pharmacokinetics of quinidine. European Journal of Clinical Pharmacology 12: 73–76 (1977).
Bonora, M.R.; Guentert, T.W.; Upton, R.A. and Riegelman, S.: Determination of quinidine and metabolites in urine by reverse-phase high-pressure liquid chromatography. Clinica Chimica Acta 91: 277–284 (1979).
Brodie, B.B. and Udenfriend, S.: The estimation of quinine in human plasma with a note on the estimation of quinidine. Journal of Pharmacology and Experimental Therapeutics 78: 154–158 (1943).
Carroll, F.I.; Smith, D; Wall, M.E. and Moreland, C.G.: Carbon-13 magnetic resonance study. Structure of the metabolites of orally administered quinidine in humans. Journal of Medicinal Chemistry 17: 985–987 (1974).
Chien, Y.W.; Lambert, H.J. and Karim, A.: Comparative binding of disopyramide phosphate and quinidine sulfate to human plasma proteins. Journal of Pharmaceutical Sciences 63: 1877–1879 (1974).
Cohen, S.I.: Current concepts in quinidine therapy; in Donoso (Ed) Drugs in Cardiology, Volume 1, pp. 17–35 (Stratton, New York 1975).
Collste, P. and Nordlander, R.: Quinidine dosage, with special reference to an oral loading dose schedule. British Journal of Clinical Pharmacology 7: 293–297 (1979).
Conn, H.L. Jr.: Quinidine as an antiarrhythmic agent Advances in Cardiopulmonary Disease 2: 286–303 (1964).
Conn, H.L. Jr. and Luchi, R.J.: Some quantitative aspects of the binding of quinidine and related quinoline compounds by human serum albumin. Journal of Clinical Investigation 40: 509–516 (1961).
Conrad, K.A.; Molk, B.L. and Chidsey, C.A.: Pharmacokinetic studies of quinidine in patients with arrhythmias. Circulation 55: 1–7 (1977).
Covinsky, J.O.; Russo, J. Jr.; Kelly, K.L.; Cashman, J.; Amick, E.N. and Mason, W.D.: Relative bioavailability of quinidine gluconate and quinidine sulfate in healthy volunteers. Journal of Clinical Pharmacology 19: 261–269 (1979).
Cramer, G. and Isaksson, B.: Quantitative determination of quinidine in plasma. Scandinavian Journal of Clinical and Laboratory Investigation 15: 553–556 (1963).
Crouthamel, W.G.: The effect of congestive heart failure on quinidine pharmacokinetics. American Heart Journal 90: 335–339 (1975).
Crouthamel, W.G.; Kowarski, B. and Narang, P.K.: Specific serum quinidine assay by high-performance liquid chromatography. Clinical Chemistry 23: 2030–2033 (1977).
Data, J.L.; Wilkinson, G.R. and Nies, A.S.: Interaction of quinidine with anticonvulsant drugs. New England Journal of Medicine 294: 699–702 (1976).
Dietmann, V.K.; Bartsch, W. and Gutekunst, M.: Untersuchungen zur antiarrhythmischen Wirkung and Toxizität von Chinidin und Dihydrochinidin sowie definierter Mischungen beider Substanzen an Ratten. Arzneimittel Forschung 27: 589 (1977).
Doering, W.: Quinidine-digoxin interaction. New England Journal of Medicine 301: 400–404 (1979).
Drayer, D.E.; Lowenthal, D.T.; Restivo, K.M.; Schwarte, A.; Cook, C.E. and Reidenberg, M.M.: Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. Clinical Pharmacology and Therapeutics 24: 31–39 (1978).
Drayer, D.E.; Restivo, K.M. and Reidenberg, M.M.: Specific determination of quinidine and (3S)-3-hydroxyquinidine in human serum by high-pressure liquid chromatography. Journal of Laboratory and Clinical Medicine 90: 816–822 (1977).
Edgar, A.L. and Sokolow, M.: Experiences with the photo-fluorometric determination of quinidine in blood. Journal of Laboratory and Clinical Medicine 36: 478–484 (1950).
Ejvinsson, G.: Effect of quinidine on plasma concentrations of digoxin. British Medical Journal 1: 279–280 (1978).
Eriksson, J.-E.; Hanson, A.; Hörlin, R.; Johansson, B.W.; Ohlsson, O.; Otto, U. and Syrén, G.: Evaluation of Quinidine Lipettes — a sustained release preparation. Acta Medica Scandinavica 205: 53–59 (1979).
Fremstad, D. and Bergerud, K.: Plasma protein binding of drugs as influenced by blood collection methods. Acta Pharmacologica et Toxicologica 39: 570–572 (1976).
Fremstad, D.; Bergerud, K.; Haffner, J.F.W. and Lunde, P.K.M.: Increased plasma binding after surgery: a preliminary report. European Journal of Clinical Pharmacology 10: 441–444 (1976).
Frigo, G.M.; Perucca, E.; Teggia-Droghi, M.; Gatti, G.; Mussini, A. and Salerno, J.: Comparison of quinidine plasma concentration curves following oral administration of some short-and long-acting formulations. British Journal of Clinical Pharmacology 4: 449–454 (1977).
Garland, W.; Trager, W.F. and Nelson, S.D.: Direct (non-chromatographic) quantification of drugs and their metabolites from human plasma utilizing chemical ionization mass spectrometry and stable isotope labeling: quinidine and lidocaine. Biomedical Mass Spectrometry 1: 124–129 (1974).
Greenblatt, D.J.; Pfeifer, H.J.; Ochs, H.R.; Franke, K.; MacLaughlin, D.S.; Smith, T.W. and Koch-Weser, J.: Pharmacokinetics of quinidine in humans after intravenous, intramuscular and oral administration. Journal of Pharmacology and Experimental Therapeutics 202: 365–378 (1977).
Greenblatt, D.J. and Woo, E.: The specificity of assays for serum or plasma quinidine. Submitted for publication (1979).
Guentert, T.W.; Coates, P.E.; Upton, R.A.; Combs, D.L. and Riegelman, S.: Determination of quinidine and its major metabolites by high-performance liquid chromatography. Journal of Chromatography 162: 59–70 (1979a).
Guentert, T.W.; Upton, R.A.; Holford, N.H.G. and Riegelman, S.: Divergence in pharmacokinetic parameters of quinidine obtained by specific and nonspecific assay methods. Journal of Pharmacokinetics and Biopharmaceutics 7: 303–311 (1979b).
Hager, W.D.; Fenster, P.; Mayersohn, M.; Perrier, D.; Graves, P.; Marcus, F.I. and Goldman, S.: Digoxin-quinidine interaction: Pharmacokinetic evaluation. New England Journal of Medicine 300: 1238–1241 (1979).
Härtel, G. and Harjaane, A.: Comparison of two methods for quinidine determination and chromatographic analysis of the difference. Clinica Chimica Acta 23: 289–294 (1969).
Härtel, G. and Korhonen, A.: Thin-layer chromatography for the quantitative separation of quinidine and quinidine metabolites from biological fluids and tissues. Journal of Chromatography 37: 70–75 (1968).
Henning, R. and Nyberg, G.: Serum quinidine levels after administration of three different quinidine preparations. European Journal of Clinical Pharmacology 6: 239–244 (1973).
Hirschfeld, D.S.; Ueda, C.T.; Rowland, M. and Scheinman, M.M.: Clinical and electrophysiological effects of intravenous quinidine in man. British Heart Journal 39: 309–316 (1977).
Hooymans, P.M. and Merkus, F.W.H.M.: Effect of quinidine on plasma concentration of digoxin. British Medical Journal 4: 1022 (1978).
Huffman, D.H. and Hignite, C.E.: Serum quinidine concentrations: comparison of fluorescence, gas-chromatographic, and gas-chromatographic/mass-spectrometric methods. Clinical Chemistry 22: 810–812 (1976).
Hughes, I.E.; Ilett, K.F. and Jellett, L.B.: The distribution of quinidine in human blood. British Journal of Clinical Pharmacology 2: 521–525 (1975).
Huynh-Ngoc, T.; Chabot, M. and Sirois, G.: Bioavailability of three commercial sustained-release tablets of quinidine in maintenance therapy. Journal of Pharmaceutical Sciences 67: 1456–1459 (1978).
Huynh-Ngoc, T. and Sirois, G.: Comparison of two spectrofluorometric procedures for quinidine determination in biological fluids. Journal of Pharmaceutical Sciences 66: 591–592 (1977).
Jaffe, J.M.; Strum, J.D.; Martineau, P.C. and Colaizzi, J.L.: Relationship between quinidine plasma and saliva levels in humans. Journal of Pharmaceutical Sciences 64: 2028–2029 (1975).
Kates, R.E.; McKennon, D.W. and Comstock, T.J.: Rapid high-pressure liquid chromatographic determination of quinidine and dihydroquinidine in plasma samples. Journal of Pharmaceutical Sciences 67: 269–270 (1978a).
Kates, R.E.; Sokoloski, T.D. and Comstock, T.J.: Binding of quinidine to plasma proteins in normal subjects and in patients with hyperlipoproteinemias. Clinical Pharmacology and Therapeutics 23: 30–35 (1978b).
Kessler, K.M.; Humphries, W.C. Jr.; Black, M. and Spann, J.F.: Quinidine pharmacokinetics in patients with cirrhosis or receiving propranolol. American Heart Journal 96: 627–635 (1978).
Kessler, K.M.; Leech, R.C. and Spann, J.F.: Blood collection techniques, heparin and quinidine protein binding. Clinical Pharmacology and Therapeutics 25: 204–210 (1979).
Kessler, K.M.; Lowenthal, D.T.; Warner, H.; Gibson, T.; Briggs, W. and Reidenberg, M.M.: Quinidine elimination in patients with congestive heart failure or poor renal function. New England Journal of Medicine 290: 706–709 (1974).
Kline, B.J.; Turner, V.A. and Barr, W.H.: Determination of quinidine and dihydroquinidine in plasma by high performance liquid chromatography. Analytical Chemistry 51: 449–451 (1979).
Leahey, E.B.; Reiffel, J.A.; Drusin, R.E.; Heissenbuttel, R.H.; Lovejoy, W.P. and Bigger, J.T.: Interaction between quinidine and digoxin. Journal of the American Medical Association 240: 533–534 (1979).
Mahon, W.A.; Mayersohn, M. and Inaba, T.: Disposition kinetics of two oral forms of quinidine. Clinical Pharmacology and Therapeutics 19: 566–575 (1976).
Mason, W.D.; Covinsky, J.O.; Valentine, J.L.; Kelly, K.L.; Weddle, O.H. and Martz, B.L.: Comparative plasma concentrations of quinidine following administration of one intramuscular and three oral formulations to 13 human subjects. Journal of Pharmaceutical Sciences 65: 1325–1329 (1976).
Midha, K.K. and Charette, C.: GLC determination of quinidine from plasma and whole blood. Journal of Pharmaceutical Sciences 63: 1244–1247 (1974).
Midha, K.K.; McGilveray, I.J.; Charette, C. and Rowe, M.L.: Comparison of a spectrofluorometric method with a gas-liquid chromatographic procedure for the determination of quinidine plasma levels. Canadian Journal of Pharmaceutical Sciences 12: 41–44 (1977).
Moulin, M.A. and Kinsun, H.: A gas-liquid chromatographic method for the quantitative determination of quinidine in blood. Clinica Chimica Acta 75: 491–495 (1977).
Nilsen, O.G.: Serum albumin and lipoproteins as the quinidine binding molecules in normal human sera. Biochemical Pharmacology 25: 1007–1012 (1976).
Nilsen, O.G. and Jacobsen, S.: The binding of quinidine to protein fractions of normal human sera. Biochemical Pharmacology 24: 995–998 (1975).
Nilsen, O.G.; Leren, P.; Aakesson, I. and Jacobsen, S.: Binding of quinidine in sera with different levels of triglycerides, cholesterol, and orosomucoid protein. Biochemical Pharmacology 27: 871–876 (1978).
Nilsen, O.G.; Storstein, L. and Jacobsen, S.: Effect of heparin and fatty acids on the binding of quinidine and warfarin in plasma. Biochemical Pharmacology 26: 229–235 (1977).
Ochs, H.R.; Greenblatt, D.J.; Woo, E.; Franke, K.; Pfeifer, H.J. and Smith, T.W.: Single and multiple dose pharmacokinetics of oral quinidine sulfate and gluconate. American Journal of Cardiology 41: 770–777 (1978b).
Ochs, H.R.; Greenblatt, D.J.; Woo, E.; Franke, K. and Smith, T.W.: Effect of propranolol on pharmacokinetics and acute electrocardiographic changes following intravenous quinidine in humans. Pharmacology 17: 301–306 (1978c).
Ochs, H.R.; Greenblatt, D.J.; Woo, E. and Smith, T.W.: Reduced quinidine clearance in elderly persons. American Journal of Cardiology 42: 481–485 (1978a).
Ochs, H.R.; Grube, E.; Greenblatt, D.J.; Woo, E. and Bodem, G.: Intravenous quinidine: pharmacokinetic properties and effects on left ventricular performance in humans. American Heart Journal. In press (1979).
Palmer, K.H.; Martin, B.; Baggett, B. and Wall, M.E.: The metabolic fate of orally administered quinidine gluconate in humans. Biochemical Pharmacology 18: 1845–1860 (1969).
Peat, M.A. and Jennison, T.A.: High-performance liquid chromatography of quinidine in plasma, with use of a microparticulate silica column. Clinical Chemistry 24: 2166–2168 (1978).
Pérez-Mateo, M. and Erill, S.: Protein binding of salicylate and quinidine in plasma from patients with renal failure, chronic liver disease and chronic respiratory insufficiency. European Journal of Clinical Pharmacology 11: 225–231 (1977).
Persson, B.-A. and Lagerström, P.-O.: Ion-pair partition chromatography in the analysis of drugs and biogenic substances in plasma and urine. Journal of Chromatography 122: 305–316 (1976).
Powers, J.L. and Sadee, W.: Determination of quinidine by high-performance liquid chromatography. Clinical Chemistry 24: 299–302 (1978).
Regårdh, C.-G.; Johnsson, G.; Lundborg, P. and Persson, B.-A.: Bioavailability of quinidine in slow-release form. Arzneimittel-Forschung 27: 1716–1718 (1977).
Reidenberg, M.M. and Affrime, M.: Influence of disease on binding of drugs to plasma proteins. Annals of the New York Academy of Sciences 226: 115–126 (1973).
Romankiewicz, J.A.; Reidenberg, M.; Drayer, D. and Franklin, J.E. Jr.: The noninterference of aluminum hydroxide gel with quinidine sulfate absorption: an approach to control quinidine-induced diarrhea. American Heart Journal 96: 518–520 (1978).
Smith, E.; Barkan, S.; Ross, B.; Maienthal, M. and Levine, J.: Examination of quinidine and quinine and their pharmaceutical preparations. Journal of Pharmaceutical Sciences 62: 1151–1155 (1973).
Smith, T.C. and Kinkel, A.W.: Bioavailability of two brands of quinidine gluconate administered on a multiple-dose regimen. Current Therapeutic Research 21: 128–134 (1977).
Soeterboek, A.M. and Van Thiel, M.: Serum quinidine levels after chronic administration of four different quinidine formulations. Journal of International Medical Research 4: 393–401 (1976).
Steyn, J.M. and Jundt, H.K.L.: A thin-layer chromatographic method for the quantitative determination of quinidine in human serum. Journal of Chromatography 111: 463–465 (1975).
Strum, J.D.; Colaizzi, J.L.; Jaffe, J.M.; Martineau, P.C. and Poust, R.I.: Comparative bioavailability of four commercial quinidine sulfate tablets. Journal of Pharmaceutical Sciences 66: 539–542 (1977).
Strum, J.D.; Ebersole, J.W.; Jaffe, J.M.; Colaizzi, J.L. and Poust, R.I.: Correlation of quinidine absorption with disintegration and dissolution rates. Journal of Pharmaceutical Sciences 67: 568 (1978).
Sved, S.; McGilveray, I.J. and Beaudoin, N.: The estimation of quinidine in human plasma by ion pair extraction and high-performance liquid chromatography. Journal of Chromatography 145: 437–444 (1978).
Török, E.; Bajkay, G.; Gulyas, A. and Makláry, E.: Comparative study of a long-acting quinidine preparation and quinidine sulphate in chronic atrial fibrillation. Pharmacologica Clinica 2: 90–93 (1970).
Ueda, C.T.; Ballard, B.E. and Rowland, M.: Concentration-time effects on quinidine disposition kinetics in rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics 200: 459–468 (1977).
Ueda, C.T. and Dzindzio, B.S.: Quinidine kinetics in congestive heart failure. Clinical Pharmacology and Therapeutics 23: 158–164 (1978).
Ueda, C.T.; Hirschfeld, D.S.; Scheinman, M.M.; Rowland, M.; Williamson, B.J. and Dzindzio, B.S.: Disposition kinetics of quinidine. Clinical Pharmacology and Therapeutics 19: 30–36 (1976a).
Ueda, C.T. and Makoid, M.C.: Quinidine and dihydroquinidine interactions in human plasma. Journal of Pharmaceutical Sciences 68: 448–450 (1979).
Ueda, C.T.; Williamson, B.J. and Dzindzio, B.S.: Absolute quinidine bioavailability. Clinical Pharmacology and Therapeutics 20: 260–265 (1976c).
Ueda, C.T.; Williamson, B.J. and Dzindzio, B.S.: Disposition kinetics of dihydroquinidine following quinidine administration. Research Communications in Chemical Pathology and Pharmacology 14: 215–225 (1976b).
Valentine, J.L.; Driscoll, P.; Hamburg, E.L. and Thompson, E.D.: GLC determination of quinidines in human plasma. Journal of Pharmaceutical Sciences 65: 96–98 (1976).
Wesley-Hadzija, B. and Mattocks, A.M.: Specific thin-layer chromatographic method for the determination of quinidine in biological fluids. Journal of Chromatography 144: 223–230 (1977).
Woo, E. and Greenblatt, D.J.: A reevaluation of intravenous quinidine. American Heart Journal 96: 829–832 (1978).
Woo, E. and Greenblatt, D.J.: Pharmacokinetic and clinical implications of quinidine protein binding. Journal of Pharmaceutical Sciences 68: 466–470 (1979).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ochs, H.R., Greenblatt, D.J. & Woo, E. Clinical Pharmacokinetics of Quinidine. Clin Pharmacokinet 5, 150–168 (1980). https://doi.org/10.2165/00003088-198005020-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198005020-00003