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Pharmacokinetic Interactions with Calcium Channel Antagonists (Part II)

  • Review Article
  • Pharmacokinetic Drug Interactions
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Summary

Since calcium channel antagonists are a diverse class of drugs frequently administered in combination with other agents, the potential for clinically significant pharmacokinetic drug interactions exists. These interactions occur most frequently via altered hepatic blood flow and impaired hepatic enzyme activity.

Part I of the article, which appeared in the previous issue of the Journal, dealt with interactions between calcium antagonists and marker compounds, theophylline, midazolam, lithium, doxorubicin, oral hypoglycaemics and cardiac drugs. Part II examines interactions with cyclosporin, anaesthetics, carbamazepine and cardiovascular agents.

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References

  • Abernethy DR, Egan JM, Dickinson TH, Carrum G. Substrate-selective inhibition by verapamil and diltiazem: differential disposition of antipyrine and theophylline in humans. Journal of Pharmacology and Experimental Therapeutics 244: 994–999, 1988

    PubMed  CAS  Google Scholar 

  • Andrejak M, Hary L, Andrejak M-T, Lesbre JP. Diltiazem increases steady state digoxin serum levels in patients with cardiac disease. Journal of Clinical Pharmacology 27: 967–970, 1987

    PubMed  CAS  Google Scholar 

  • Bach D, Blevins R, Kerner N, Rubenfire M, Edwards DJ. The effect of verapamil on antipyrine pharmacokinetics and metabolism in man. British Journal of Clinical Pharmacology 21: 655–659, 1986

    PubMed  CAS  Google Scholar 

  • Baeyens JM, Del Pozo E. Interactions between calcium channel blockers and non-cardiovascular drugs: interactions with drugs acting at the neuromuscular or the CNS level. Pharmacology and Toxicology 62: 59–63, 1988

    PubMed  CAS  Google Scholar 

  • Bauer LA, Stenwall M, Horn JR, Davis R, Opheim K, et al. Changes in antipyrine and indocyanine green kinetics during nifedipine, verapamil and diltiazem therapy. Clinical Pharmacology and Therapeutics 40: 239–242, 1986

    PubMed  CAS  Google Scholar 

  • Beattie B, Biller J, Melhaus B, Murray M. Verapamil-induced carbamazepine neurotoxicity. European Neurology 28: 104–105, 1988

    PubMed  CAS  Google Scholar 

  • Bell PF, Mirkakhur RK, Elliott P. Onset and duration of clinical relaxation of atracurium and vecuronium in patients on chronic nifedipine therapy. European Journal of Anaesthesiology 6: 343–346, 1989

    PubMed  CAS  Google Scholar 

  • Beltrami TR, May JJ, Bertino JS. Lack of effects of diltiazem on digoxin pharmacokinetics. Journal of Clinical Pharmacology 25: 390–392, 1985

    PubMed  CAS  Google Scholar 

  • Belz GG, Doering W, Munkes R, Matthews J. Interaction between digoxin and calcium antagonists and antiarrhythmic drugs. Clinical Pharmacology and Therapeutics 33: 410–417, 1983

    PubMed  CAS  Google Scholar 

  • Belz GG, Wistuba S, Matthews JH. Digoxin and bepridil: pharmacokinetic and pharmacodynamic interactions. Clinical Pharmacology and Therapeutics 39: 65–71, 1986

    PubMed  CAS  Google Scholar 

  • Borel JF, Feuer C, Magnee C, Stahelin H. Effects of the new anti-lymphocyte peptide cyclospirin A in animals. Immunology 32: 1017–1025, 1977

    PubMed  CAS  Google Scholar 

  • Bottorff MB, Lalonde RL, Kazierad DJ, Hoon TJ, Tsiu SJ, et al. The effects of encainide versus diltiazem on the oxidative metabolic pathways of antipyrine. Pharmacotherapy 9: 315–321, 1989

    PubMed  CAS  Google Scholar 

  • Bourbigot B, Guiserix J, Airiau J, Bressollette L, Morin JF, et al. Nicardipine increases cyclosporine blood levels. Lancet 1: 1447, 1986

    PubMed  CAS  Google Scholar 

  • Bratel T, Billings B, Dahlqvist R. Felodipine reduces the absorption of theophylline in man. European Journal of Clinical Pharmacology 36: 481–485, 1989

    PubMed  CAS  Google Scholar 

  • Brodie MJ, Macphee GJA. Carbamazepine neurotoxicity precipitated by diltiazem. British Medical Journal 292: 1170–1171, 1986

    PubMed  CAS  Google Scholar 

  • Burnakis TG, Seldon M, Czaplicki AD. Increased serum theophylline concentrations secondary to oral verapamil. Clinical Pharmacy 2: 458–461, 1983

    PubMed  CAS  Google Scholar 

  • Cantrovich M, Hiesse C, Lockiec F, Charpenter B, Fries D. Confirmation of the interaction between cyclosporine and the calcium channel blocker nicardipine in renal transplant patients. Clinical Nephrology 28: 190–193, 1987

    Google Scholar 

  • Carrum G, Egan JM, Abernethy DR. Diltiazem treatment impairs hepatic drug oxidation: studies of antipyrine. Clinical Pharmacology and Therapeutics 40: 140–143, 1986

    PubMed  CAS  Google Scholar 

  • Carruthers SG, Bailey DG. Tolerance and cardiovascular effects of single dose felodipine/beta-blocker combinations in healthy subjects. Journal of Cardiovascular Pharmacology 10 (Suppl. 1): S169–S177, 1987

    PubMed  CAS  Google Scholar 

  • Carruthers SG, Freeman DJ, Bailey DG. Synergistic adverse hemodynamic interaction between oral verapamil and propranolol. Clinical Pharmacology and Therapeutics 46: 469–477, 1989

    PubMed  CAS  Google Scholar 

  • Chelly JE, Hill DC, Abernethy DR, Dlewati A, Doursout F, et al. Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil. Journal of Pharmacology and Experimental Therapeutics 243: 211–216, 1987b

    PubMed  CAS  Google Scholar 

  • Chelly JE, Hysing ES, Abernethy DR, Doursout M, Hartley CJ, et al. Role of isoflurane on hemodynamic properties and disposition of nicardipine. Journal of Pharmacology and Experimental Therapeutics 241: 899–906, 1987a

    PubMed  CAS  Google Scholar 

  • Connacher AA, Debani AHE, Isles TE, Stevenson IH. Disposition and hypoglycaemic action of glipizide in diabetic patients given a single dose of nifedipine. European Journal of Clinical Pharmacology 33: 81–83, 1987

    PubMed  CAS  Google Scholar 

  • Copur MS, Tasdemir I, Turgan C, Yasavul U, Caglar S. Effects of nitrendipine on blood pressure and blood cyclosporin a level in patients with posttransplant hypertension. Nephron 52: 227–230, 1989

    PubMed  CAS  Google Scholar 

  • Danhof M, van Zuilen A, Boeijinga JK, Breimer DD. Studies of the different metabolic pathways of antipyrine in man: oral vs i.v. administration and the influence of urinary collection time. European Journal of Clinical Pharmacology 21: 433–441, 1982

    PubMed  CAS  Google Scholar 

  • Debruyne D, Commeau P, Grollier H, Huret B, Scanu P, et al. Nicardipine does not significantly affect serum digoxin concentrations at the steady state of patients with congestive heart failure. International Journal of Pharmaceutical Research 9: 15–19, 1989

    CAS  Google Scholar 

  • Deray G, Aupetit B, Martinez F, Baumelou A, Worcel A, et al. Cyclosporine-nicardipine interaction. American Journal of Nephrology 9: 349, 1989

    PubMed  CAS  Google Scholar 

  • Doering W. Effect of coadministration of verapamil and quinidine on serum digoxin concentration. European Journal of Clinical Pharmacology 25: 517–521, 1983

    PubMed  CAS  Google Scholar 

  • Dreyfuss M, Harri E, Hofman H, Kobel H, Pache W, et al. Cyclosporin A and C. New metabolites from Trichoderma polysporum (Link ex Pers) Rifai. European Journal of Applied Microbiology 3: 125–133, 1976

    CAS  Google Scholar 

  • Dubovsky SL, Franks RD, Allen S. Verapamil: a new antimanic drug with potential interactions with lithium Journal of Clinical Psychiatry 48: 371–372, 1987

    PubMed  CAS  Google Scholar 

  • Dunselman PHJM, Scaf AHJ, Kuntze CEE, Lie KI, Wesseling H. Digoxin-felodipine interactions in patients with congestive heart failure. European Journal of Clinical Pharmacology 35: 461–465, 1988

    PubMed  CAS  Google Scholar 

  • Edwards DJ, Lavoie R, Beckman H, Blevins R, Rubenfire M. The effect of coadministration of verapamil on the pharmacokinetics and metabolism of quinidine. Clinical Pharmacology and Therapeutics 41: 68–73, 1987

    PubMed  CAS  Google Scholar 

  • Eimer M, Carter BL. Elevated serum carbamazepine concentrations following diltiazem initiation. Drug Intelligence and Clinical Pharmacy 21: 340–342, 1987

    PubMed  CAS  Google Scholar 

  • Elliott HL, Meredith PA, Campbell L, Reid JL. The combination of prazosin and verapamil in the treatment of hypertension. Clinical Pharmacology and Therapeutics 43: 554–560, 1988

    PubMed  CAS  Google Scholar 

  • Farringer JA, Green JA, O’Rourke RA, Linn WA, Clementi WA. Nifedipine-induced alterations in serum quinidine concentrations. American Heart Journal 108: 1570–1572, 1984

    PubMed  CAS  Google Scholar 

  • Gangji D, Juvent M, Niset G, Wathieu M, Degreve M, et al. Study of the influence of nifedipine on the pharmacokinetics and pharmacodynamics of propranolol, metoprolol, and atenolol. British Journal of Clinical Pharmacology 17: 29S–35S, 1984

    PubMed  Google Scholar 

  • Garty M, Cohen E, Mazar A, Ilfeld DN, Spitzer S, et al. Effect of nifedipine and theophylline in asthma. Clinical Pharmacology and Therapeutics 40: 195–198, 1986b

    PubMed  CAS  Google Scholar 

  • Garty M, Shamir E, Ilfeld D, Pitlik S, Rosenfeld JB. Non interaction of digoxin and nifedipine in cardiac patients. Journal of Clinical Pharmacology 26: 304–305, 1986a

    PubMed  CAS  Google Scholar 

  • Gin AS, Stringer KA, Welage LS, Wilten JH, Matthews GE. The effect of verapamil on the pharmacokinetic disposition of theophylline in cigarette smokers. Journal of Clinical Pharmacology 29: 728–732, 1989

    PubMed  CAS  Google Scholar 

  • Grainger SL, Keeling PWN, Brown IMH, Marigold JH, Thompson RPH. Clearance and noninvasive determination of the hepatic extraction of indocyanine green in baboons and man. Clinical Science 64: 207–212, 1983

    PubMed  CAS  Google Scholar 

  • Green JA, Clemanti WA, Porter C, Stigelman W. Nifedipinequinidine interaction. Clinical Pharmacy 2: 461–465, 1983

    PubMed  CAS  Google Scholar 

  • Grino JM, Sabate I, Castelao AM, Alsina J. Influence of diltiazem on cyclosporin clearance. Lancet 1: 1387, 1986

    PubMed  CAS  Google Scholar 

  • Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, et al. Characterization of the rat and human microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidatiave drug metabolism. Journal of Biological Chemistry 261: 5051–5060, 1986b

    PubMed  CAS  Google Scholar 

  • Guengerich FP, Muller-Enoch D, Blair IA. Oxidation of quinidine by human liver cytochrome P-450. Molecular Pharmacology 30: 287–295, 1986a

    PubMed  CAS  Google Scholar 

  • Hamman S, Todd G, McAllister R. The pharmacology of verapamil. Pharmacology 27: 1, 1983

    Google Scholar 

  • Handel J, Ziegler G, Gemeinhardt A, Stuber H, Fischer C, et al. Lack of effect of nitrendipine on the pharmacokinetics and pharmacodynamics of midazolam during steady state. British Journal of Clinical Pharmacology 25: 243–250, 1988

    PubMed  CAS  Google Scholar 

  • Hantler CH, Wilton N, Learned DM, Hill AEG, Knight PR. Impaired myocardial conduction in patients receiving diltiazem therapy during enflurane anesthesia. Anesthesiology 67: 94–96, 1987

    PubMed  CAS  Google Scholar 

  • Harrod CS. Theophylline toxicity and nifedipine Correspondence. Annals of Internal Medicine 106: 480, 1987

    PubMed  CAS  Google Scholar 

  • Henricsson S, Lindholm A. Inhibition of cyclosporine metabolism by other drugs in vitro. Transplantation Proceedings 20: 569–571, 1988

    PubMed  CAS  Google Scholar 

  • Höglund P, Nilsson LG. Pharmacokinetics of diltiazem and its metabolites after single and multiple dosing in healthy volunteers. Therapeutic Drug Monitoring 11: 558–566, 1989

    PubMed  Google Scholar 

  • Holtzman JL, Finley D, Mottonen L, Berry DA, Ekholm BP, et al. The pharmacodynamic and pharmacokinetic interaction between single doses of flecainide acetate and verapamil: effects on cardiac function and drug clearance. Clinical Pharmacology and Therapeutics 46: 26–32, 1989

    PubMed  CAS  Google Scholar 

  • Hunt BA, Bottorff MB, Herring VL, Self TH, Lalonde RL. Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers. Clinical Pharmacology and Therapeutics 47: 584–591, 1990

    PubMed  Google Scholar 

  • Jackson SHD, Shah K, Debbas NMG, Johnston A, Peverel-Cooper CA, et al. The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers. British Journal of Clinical Pharmacology 21: 389–392, 1986

    PubMed  CAS  Google Scholar 

  • Jee LD, Opie LH. Acute hypotensive response to nifedipine added to prazosin in treatment of hypertension. British Medical Journal 287: 1514, 1983

    PubMed  CAS  Google Scholar 

  • Johnson BF, Wilson J, Marwaha R, Hoch K, Johnson J. The comparative effects of verapamil and a new dihydropyridine calcium channel blocker on digoxin pharmacokinetics. Clinical Pharmacology and Therapeutics 42: 66–67, 1987

    PubMed  CAS  Google Scholar 

  • Jones WN, Kern KB, Rindone JP, Mayersohn M, Bliss M, et al. Digoxin-diltiazem interaction: a pharmacokinetic evaluation. European Journal of Clinical Pharmacology 31: 351–353, 1986

    PubMed  CAS  Google Scholar 

  • Kahan BD. Cyclosporine. New England Journal of Medicine 321: 1725–1738, 1989

    PubMed  CAS  Google Scholar 

  • Kalra L, Bone MF, Ariaraj SJP. Nifedipine-aminophylline interaction. Journal of Clinical Pharmacology 28: 1056–1057, 1988

    PubMed  CAS  Google Scholar 

  • Kapur PA, Grogan DL, Fournier DJ. Cardiovascular interactions of lidocaine with verapamil or diltiazem in the dog. Anesthesiology 68: 79–85, 1988

    PubMed  CAS  Google Scholar 

  • Kazierad DJ, Lalonde RL, Hoon TJ, Mirvis DM, Bottorff MB. The effect of diltiazem on the disposition of encainide and its active metabolites. Clinical Pharmacology and Therapeutics 46: 668–673, 1989

    PubMed  CAS  Google Scholar 

  • Keech AC, Harper RW, Harrison PM, Pitt A, McLean AJ. Pharmacokinetic interaction between oral metoprolol and verpamil for angina pectoris. American Journal of Cardiology 58: 551–552, 1986

    PubMed  CAS  Google Scholar 

  • Keech AC, Harper RW, Harrison PM, Pitt A, McLean AJ. Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interactions in man. European Journal of Clinical Pharmacology 35: 363–366, 1988

    PubMed  CAS  Google Scholar 

  • Kendall MJ, Jack DB, Laugher SJ, Lobo J, Smith SR. Lack of a pharmacokinetic interaction between nifedipine and the beta-adrenoceptor blockers metoprolol and atenolol. British Journal of Clinical Pharmacology 18: 331–335, 1984

    PubMed  CAS  Google Scholar 

  • Kerr DJ, Graham J, Cummings J, Morrison JG, Thompson GG, et al. The effect of verapamil on the pharmacokinetics of adriamycin. Cancer Chemotherapy and Pharmacology 18: 239–242, 1986

    PubMed  CAS  Google Scholar 

  • Kessler M, Netter P, Renoult E, Jonon B, Mur JM, et al. Influence of nicardipine on renal function and plasma cyclosporine in renal transplant patients. European Journal of Clinical Pharmacology 36: 637–638, 1989

    PubMed  CAS  Google Scholar 

  • Kirch W, Hutt HJ, Dylewicz P, Graf KJ, Ohnhaus EE. Dose-dependence of the nifedipine-digoxin interaction? Clinical Pharmacology and Therapeutics 39: 35–39, 1986c

    PubMed  CAS  Google Scholar 

  • Kirch W, Logemann C, Heidemann H, Santos SR, Ohnhaus EE. Effects of two different doses of nitrendipine on steady-state plasma digoxin level and systolic time intervals. European Journal of Clinical Pharmacology 31: 391–395, 1986a

    PubMed  CAS  Google Scholar 

  • Kirch W, Stenzel J, Dylewicz P, Hutt HJ, Santos SR, et al. Influence of nisoldipine on haemodynamic effects and plasma levels of digoxin. British Journal of Clinical Pharmacology 232: 155–159, 1986b

    Google Scholar 

  • Kleinbloesem BH, van Brummelen P, Hillers J, Moolenaar AJ, Breimer DD. Interaction between digoxin and nifedipine at steady state in patients with atrial fibrillation. Therapeutic Drug Monitoring 7: 372–376, 1985

    PubMed  CAS  Google Scholar 

  • Klockowski P, Lener M, Sirgo MA, Rocci ML. Comparative effects of isradipine and diltiazem on antipyrine and indocyanine green clearances in elderly volunteers. Clinical Pharmacology and Therapeutics 48: 375–380, 1990

    PubMed  CAS  Google Scholar 

  • Kohlhaw K, Wonigeit K, Frei U, Oldhafer K, Neuman K, et al. Effect of the calcium channel blocker diltiazem on cyclosporine A blood levels and dose requirements. Transplantation Proceedings 20: 572–574, 1988

    PubMed  CAS  Google Scholar 

  • Koren G, Zylber-Katz E, Granit L, Levy M. Pharmacokinetic studies of nifedipine and digoxin co-administration. International Journal of Clinical Pharmacology Therapy and Toxicology 24: 39–42, 1986

    CAS  Google Scholar 

  • Kounis NG. Asystole after verapamil and digoxin. British Journal of Clinical Practice 34: 57–58, 1980

    PubMed  CAS  Google Scholar 

  • Kuhlmann J. Effects of nifedipine and diltiazem on plasma levels and renal excretion of beta-acetyldigoxin. Clinical Pharmacology and Therapeutics 37: 150–156, 1985a

    PubMed  CAS  Google Scholar 

  • Kuhlmann J. Effects of verapamil, diltiazem and nifedipine on plasma levels and renal excretion of digitoxin. Clinical Pharmacology and Therapeutics 38: 667–673, 1985b

    PubMed  CAS  Google Scholar 

  • Kuhlmann J. Effects of quinidine, verapamil and nifedipine on the pharmacokinetics and pharmacodynamics of digitoxin during steady state conditions. Arzneimittel-Forschung 37: 545–548, 1987

    PubMed  CAS  Google Scholar 

  • Lees KR, Reid JL. Lisinopril and nifedipine: no acute interaction in normotensives. British Journal of Clinical Pharmacology 25: 307–313, 1988

    PubMed  CAS  Google Scholar 

  • Lessem J, Bellinetto A. Interaction between digoxin and the calcium antagonists nicardipine and tiapamil. Clinical Therapeutics 5: 595–602, 1983

    PubMed  CAS  Google Scholar 

  • Levine MAH, Ogilvie RI, Leenen FHH. Pharmaockinetic and pharmacodynamic interactions between nisoldipine and propranolol. Clinical Pharmacology and Therapeutics 43: 39–48, 1988

    PubMed  CAS  Google Scholar 

  • Lindholm A, Henricsson S. Verapamil inhibits cyclosporine metabolism. Lancet 1: 1262–1263, 1987

    PubMed  CAS  Google Scholar 

  • Macphee GJA, Thompson GG, McInnes GT, Brodie MJ. Verapamil potentiates carbamazepine neurotoxicity: a clinically important inhibitory interaction. Lancet 1: 700–703, 1986

    PubMed  CAS  Google Scholar 

  • Maggio TG, Bartels DW. Increased cyclosporine blood concentrations due to verapamil administration. Drug Intelligence and Clinical Pharmacy 22: 705–707, 1988

    PubMed  CAS  Google Scholar 

  • Maragno L, Gianotti C,. Tropeano PF, Rodighiero V, Gaion RM, et al. Verapamil-induced changes in digoxin kinetics in cirrhosis. European Journal of Clinical Pharmacology 32: 309–311, 1987

    PubMed  CAS  Google Scholar 

  • Maurer G, Lemaire M. Biotransformation and distribution in blood of cyclosporine and its metabolites. Transplantation Proceedings 18: 25–34, 1986

    PubMed  CAS  Google Scholar 

  • McAinsh J, Holmes BF, Smith S, Hood D, Warren D. Atenolol kinetics in renal failure. Clinical Pharmacology and Therapeutics 28: 302–309, 1980

    PubMed  CAS  Google Scholar 

  • McAllister CB, Wolfenden HT, Aslanian WS, Woosley RL, Wilkinson GR. Oxidative metabolism of encainide: polymorphism, pharmacokinetics, and clinical considerations. Xenobiotica 16: 483–490, 1986

    PubMed  CAS  Google Scholar 

  • McCourty JC, Silas JH, Tucker GT, Lennard MS. The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris. British Journal of Clinical Pharmacology 25: 349–357, 1988

    PubMed  CAS  Google Scholar 

  • McLean AJ, Knight R, Harrison PM, Harper RW. Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol. American Journal of Cardiology 55: 55: 1628–1629, 1985

    PubMed  CAS  Google Scholar 

  • McNally P, Mistry N, Idle J, Walls J, Feehally J. Calcium channel blockers and cyclosporine metabolism. Transplantation 48: 1071, 1989

    PubMed  CAS  Google Scholar 

  • Meredith PA, Elliott HL, Pasanisi F, Kelman AW, Sumner DJ, et al. Verapamil pharmacokinetics and apparent hepatic and renal blood flow. British Journal of Clinical Pharmacology 20: 101–106, 1985a

    PubMed  CAS  Google Scholar 

  • Meredith PA, Pasanisi F, Elliott HL, Reid JL. The effect of nisoldipine on apparent liver blood flow and effective renal plasma flow. British Journal of Clinical Pharmacology 20: 235–237, 1985b

    PubMed  CAS  Google Scholar 

  • Merin RG. Cardiac arrest following i.v. verapamil may be related to concomitant digoxin therapy as well as halothane. British Journal of Anaesthesia 61: 366, 1988

    PubMed  CAS  Google Scholar 

  • Miners JO, Smith KJ, Robson RA, McManus ME, Veronese ME, et al. Tolbutamide hydroxylation by human liver microsomes. Biochemical Pharmacology 37: 1137–1144, 1988

    PubMed  CAS  Google Scholar 

  • Moller IW, Cardiac arrest following i.v. verapamil combined with halothane anaesthesia. British Journal of Anaesthesia 59: 522–523, 1987

    PubMed  CAS  Google Scholar 

  • Muller H, Kafurke H, Marck P, Zierski J, Hempelmann G. Interactions between nimodipine and general anesthesia — clinical investigations in 124 patients during neurosurgical operations. Acta Neurochirurgica S45: 29–35, 1988

    Google Scholar 

  • Munger MA, Jarvis RC, Nair R, Kasmer RJ, Nara AR, et al. Elucidation of the nifedipine-quinidine interaction. Clinical Pharmacology and Therapeutics 45: 411–416, 1989

    PubMed  CAS  Google Scholar 

  • Nafzinger AN, May JJ, Bertino JS. Inhibition of theophylline elimination by diltiazem therapy. Journal of Clinical Pharmacology 27: 862–865, 1987

    Google Scholar 

  • Nebert DW, Nelson DR, Adesnik M, Coon MJ, Estabrook RW, et al. The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. DNA and Cell Biology 8: 1–13, 1989

    CAS  Google Scholar 

  • Neumayer HH, Wagner K. Diltiazem and economic use of cyclosporin. Lancet 2: 523, 1986

    PubMed  CAS  Google Scholar 

  • North DS, Mattern AL, Hiser WW. The influence of diltiazem hydrochloride on trough serum digoxin concentrations. Drug Intelligence and Clinical Pharmacy 20: 500–503, 1986

    PubMed  CAS  Google Scholar 

  • Opie LH, Buhler FR, Fleckenstein A, Hansson L, Harrison DC, et al. International Society and Federation of Cardiology: working group on classification of calcium antagonists for cardiovascular disease. American Journal of Cardiology 60: 630–632, 1987

    PubMed  CAS  Google Scholar 

  • Oyama Y, Fujii S, Kanda K, Akino E, Kawasaki H, et al. Digoxin-diltiazem interaction. American Journal of Cardiology 53: 1480–1481, 1984

    PubMed  CAS  Google Scholar 

  • Parrillo SJ. Elevated theophylline blood levels from institution of nifedipine therapy. Annals of Emergency Medicine 13: 216–217, 1984

    PubMed  CAS  Google Scholar 

  • Pasanisi F, Elliott HL, Meredith PA, McSharry DR, Reid JL. Combined alpha adrenoceptor antagonism and calcium channel blockade in normal subjects. Clinical Pharmacology and Therapeutics 36: 716–723, 1984

    PubMed  CAS  Google Scholar 

  • Pasanisi F, Elliott HL, Meredith PA, Sumner DJ, Reid JL. Effects of calcium channel blockers on adrenergic and non-adrenergic vascular responses in man. Journal of Cardiovascular Pharmacology 7: 1166–1170, 1985

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pederson A, Hvidt S, Klitgaard NA, Kjaer K, et al. Effect of nifedipine on digoxin kinetics in healthy subjects. Clinical Pharmacology and Therapeutics 32: 562–565, 1982a

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pederson A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F. Digoxin-verapamil interaction. Clinical Pharmacology and Therapeutics 30: 311–316, 1981

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Dorph-Pederson A, Hvidt S, Klitgaard NA, Nielsen-Kudsk F. The long-term effect of verapamil on plasma digoxin concentration and renal digoxin clearance in healthy subjects. European Journal of Clinical Pharmacology 22: 123–127, 1982b

    PubMed  CAS  Google Scholar 

  • Pedersen KE, Madsen JL, Klitgaard NA, Kjaer K, Hvidt S. Noninteraction between nifedipine and digoxin. Danish Medical Bulletin 33: 109–110, 1986

    PubMed  CAS  Google Scholar 

  • Piepho RW, Sowers JR. Antihypertensive therapy in the geriatric patient I. A review of the role of calcium channel blockers. Journal of Clinical Pharmacology 29: 193–204, 1989

    PubMed  CAS  Google Scholar 

  • Pochet JM, Pirson Y. Cyclosporin-diltiazem interaction. Lancet 1: 979, 1986

    PubMed  CAS  Google Scholar 

  • Price WA, Shalley JE. Lithium-verapamil toxicity in the elderly. Journal of the American Geriatric Society 35: 177–178, 1987

    CAS  Google Scholar 

  • Ptachcinski J, Hakala T, Tzakis A, Burkhart G, Venkataramanan R. Diltiazem-induced increase in cyclosporine blood concentrations. Pharmacotherapy 8: 138, 1988

    Google Scholar 

  • Ptazschke K, Duhme B, Maul W. Pharmacokinetics of adalat in animal experiments. In Lochner et al. (Eds) Second International Adalat Symposium, p. 27, Springer, New York, 1975

    Google Scholar 

  • Rameis H, Magometschnigg D, Ganzinger U. The diltiazem-digoxin interaction. Clinical Pharmacology and Therapeutics 36: 183–189, 1984

    PubMed  CAS  Google Scholar 

  • Ramsay JF, Cutfield GR, Francis CM, Devlin WH, Foex P. Halothane-verapamil causes regional myocardial dysfunction in the dog. British Journal of Anaesthesia 58: 321–326, 1986

    PubMed  CAS  Google Scholar 

  • Renton KW. Inhibition of hepatic microsomal drug metabolism by the calcium channel blockers diltiazem and verapamil. Biochemical Pharmacology 34: 2549–2553, 1985

    PubMed  CAS  Google Scholar 

  • Reves JG, Kissin IG, Lell WA, Tosone S. Calcium entry blockers: uses and implications for anesthesiologists. Anesthesiology 57: 504–518, 1982

    PubMed  CAS  Google Scholar 

  • Robson RA, Frankel M, Barratt LJ, Birkett DJ. Cyclosporin-verapamil interaction. British Journal of Clinical Pharmacology 25: 401–402, 1988a

    Google Scholar 

  • Robson RA, Miners JO, Birkett DJ. Selective inhibitor effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline. British Journal of Clinical Pharmacology 25: 397–400, 1988b

    PubMed  CAS  Google Scholar 

  • Rodin SM, Johnson BF, Wilson J, Ritchie P, Johnson J. Comparative effects of verapamil and isradipine on steady-state digoxin kinetics. Clinical Pharmacology and Therapeutics 43: 668–672, 1988

    PubMed  CAS  Google Scholar 

  • Rosenkranz B, Ledermann H, Frolich JC. Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers. Journal of Cardiovascular Pharmacology 5: 943–949. 1986

    Google Scholar 

  • Rubin AS, Zablocki AD. Hyperkalemia, verapamil, and dantrolene. Anesthesiology 66: 246–249, 1987

    PubMed  CAS  Google Scholar 

  • Rumiantsev DO, Piotrovskii VK, Riabokon OS, Slastnikova ID, Kokurina EV, et al. The effect of oral verapamil therapy on antipyrine clearance. British Journal of Clinical Pharmacology 22: 606–609, 1986

    PubMed  CAS  Google Scholar 

  • Sabate I, Grino JM, Castelao AM, Huguet J, Seron D, et al. Cyclosporin-diltiazem interaction: comparison of cyclosporin levels measured with two monoclonal antibodies. Transplantation Proceedings 21: 1460–1461, 1989

    PubMed  CAS  Google Scholar 

  • Sabate I, Grino J, Castelao AM, Ortola J. Evaluation of cyclosporin-verapamil interaction, with observations on parent cyclosporin and metabolites. Clinical Chemistry 34: 2151, 1988

    PubMed  CAS  Google Scholar 

  • Schwartz JB. Effects of amlodipine on steady-state digoxin concentration and renal digoxin clearance. Journal of Cardiovascular Pharmacology 12: 1–5, 1988

    PubMed  CAS  Google Scholar 

  • Schwartz JB, Keefe DL, Kirsten E, Kates RE, Harrison DC. Prolongation of verapamil elimination kinetics during chronic oral dosing. American Heart Journal 104: 198–203, 1982

    PubMed  CAS  Google Scholar 

  • Schwartz JB, Migliore PJ. Effect of nifedipine on serum digoxin concentration and renal digoxin clearance. Clinical Pharmacology and Therapeutics 36: 19–24, 1984a

    PubMed  CAS  Google Scholar 

  • Schwartz JB, Raizner A, Akers S. The effect of nifedipine on serum digoxin concentrations in patients. American Heart Journal 107: 669–673, 1984b

    PubMed  CAS  Google Scholar 

  • Shand DG, Hammill SC, Aanonsen L, Pritchett ELC. Reduced verapamil clearance during long-term oral administration. Clinical Pharmacology and Therapeutics 30: 701–703, 1981

    PubMed  CAS  Google Scholar 

  • Sirmans SM, Pieper JA, Lalonde RL, Smith DG, Self TH. Effect of calcium channel blockers on theophylline disposition. Clinical Pharmacology and Therapeutics 44: 29–34, 1988

    PubMed  CAS  Google Scholar 

  • Smith SR, Haffner CA, Kendall MJ. The influence of nifedipine and diltiazem on serum theophylline concentration-time profiles. Journal of Clinical Pharmacy and Therapeutics 14: 403–408, 1989

    PubMed  CAS  Google Scholar 

  • Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S. Pharmacokinetic interactions between felodipine and metoprolol. European Journal of Clinical Pharmacology 31: 575–578, 1987

    PubMed  CAS  Google Scholar 

  • Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. American Journal of Obstetrics and Gynecology 161: 35–36, 1989

    PubMed  CAS  Google Scholar 

  • Tallman RD, Rosenblatt RM, Weaver JM, Wang Y. Verapamil increases the toxicity of local anesthetics. Journal of Clinical Pharmacology 28: 317–321, 1988

    PubMed  CAS  Google Scholar 

  • Trohnman RG, Estes DM, Castellanos A, Palomo AR, Myerburg RJ, et al. Increased quinidine plasma concentrations during administration of verapamil: a new quinidine-verapamil interaction. American Journal of Cardiology 57: 706–707, 1986

    Google Scholar 

  • Valdiserri EV. A possible interaction between lithium and diltiazem. Journal of Clinical Psychiatry 46: 540–541, 1985

    PubMed  CAS  Google Scholar 

  • Vanhoutte PM. The expert committee of the World Health Organization on classification of calcium antagonists: the viewpoint of the raporteur. American Journal of Cardiology 59: 3A–8A, 1987

    PubMed  CAS  Google Scholar 

  • VanLith RM, Appleby DH. Quinidine-nifedipine interaction. Drug Intelligence and Clinical Pharmacy 19: 829–831, 1985

    CAS  Google Scholar 

  • Vesell ES. The antipyrine test in clinical pharmacology: conceptions and misconceptions. Clinical Pharmacology and Therapeutics 26: 275–286, 1979

    PubMed  CAS  Google Scholar 

  • Vinceneux P, Canal M, Domart Y, Roux A, Cascio B, et al. Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol. International Journal of Clinical Pharmacology Therapy and Toxicology 24: 153–158, 1986

    CAS  Google Scholar 

  • Wadhwa N, Schroeder T, O’Flaherty E, Pesce A, Myre S, et al. The effect of oral metoclopramide on the absorption of oral cyclosporine. Transplantation 43: 211–214, 1987b

    PubMed  CAS  Google Scholar 

  • Wadhwa N, Schroeder T, Pesce A, Myre S, Clardy C, et al. Cyclosporine drug interactions: a review. Therapeutic Drug Monitoring 9: 399–406, 1987a

    PubMed  CAS  Google Scholar 

  • Wagner K, Albrecht S, Neumayer HH. Prevention of posttransplant acute tubular necrosis by the calcium antagonist diltiazem: a prospective randomized study. American Journal of Nephrology 7: 287–291, 1987

    PubMed  CAS  Google Scholar 

  • Wagner K, Neumayer HH. Prevention of delayed graft function in cadaver kidney transplants by diltiazem. Lancet 1: 1355–1356, 1985

    Google Scholar 

  • Wagner K, Philipp T, Heinemeyer F, Brockmuller F, Roots I, et al. Interaction of cyclosporin and calcium antagonists. Transplantation Proceedings 21: 1453–1456, 1989

    PubMed  CAS  Google Scholar 

  • Wali FA. Interaction of verapamil with gallamine and pancuronium and reversal of combined neuromuscular blockade with neostigmine and edrophonium. European Journal of Anaesthesiology 3: 385–393, 1986

    PubMed  CAS  Google Scholar 

  • Walz G, Kunzendorf U, Keller F, Neumayer HH, Offermann G,. Cyclosporine blood levels in diltiazem-treated patients. Clinical Transplantation 2: 21–25, 1988

    Google Scholar 

  • Wang T, Roden DM, Wolfendan HT, Woosley RL, Wood AJJ, et al. Influence of genetic polymorphism on the metabolism and disposition of encainide in man. Journal of Pharmacology and Experimental Therapeutics 228: 605–611, 1984

    PubMed  CAS  Google Scholar 

  • Wilkinson GR, Shand DG. A physiologic approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390, 1975

    PubMed  CAS  Google Scholar 

  • Winkle RA, Peters F, Kates RE, Harrison DC. Possible contribution of encainide metabolites to the long-term antiarrhythmic efficacy of encainide. American Journal of Cardiology 51: 1182–1188, 1983

    PubMed  CAS  Google Scholar 

  • Yoshida A, Fujita M, Kurosawa N, Nioka M, Shichonohe T, et al. Effects of diltiazem on plasma level and urinary excretion of digoxin in healthy subjects. Clinical Pharmacology and Therapeutics 35: 681–685, 1984

    PubMed  CAS  Google Scholar 

  • Zaggy AP, Kates RA, Norfleet EA, Mueller RA, Heath KR. The comparative cardiovascular effects of verapamil, nifedipine, and diltiazem during halothane anesthesia. Anesthesiology 59: A44, 1983

    Google Scholar 

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  1. Division of Clinical and Hospital Pharmacy, University of Cincinnati Medical Center, College of Pharmacy, Mail Location #4, Cincinnati, Ohio, 45267, USA

    Karen D. Schlanz, Steven A. Myre &  Michael B. Bottorff

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  1. Karen D. Schlanz
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Schlanz, K.D., Myre, S.A. & Bottorff, M.B. Pharmacokinetic Interactions with Calcium Channel Antagonists (Part II). Clin. Pharmacokinet. 21, 448–460 (1991). https://doi.org/10.2165/00003088-199121060-00005

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