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Verapamil disposition and cardiovascular effects in elderly patients after single intravenous and oral doses

  • Calcium Antagonists
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Summary

Pharmacokinetics and pharmacodynamics of verapamil were studied in 11 elderly subjects (age=79.67±4.74 years) and in 11 middle-aged subjects (age=45±11.37 years) following intravenous (IV), single oral, and long-term oral administration.

Plasma verapamil concentrations were determined using high-pressure liquid chromatography (HPLC). Twenty-four hour dynamic Holter electrocardiographic (ECG) recordings were employed to study heart rate (HR) and P-R interval.

No difference in plasma half-life, distribution volume, body clearance, and area under the curve (AUC) was observed between the two groups after IV and oral verapamil administration.

Blood pressure (BP) and HR were significantly reduced after verapamil IV administration in the elderly group only (p<0.05, p<0.01, respectively). After single and long-term oral administration, variable HR and BP responses were observed in both groups.

The P-R prolongation following both IV and single oral doses exhibited a delay with respect to the peak plasma concentration, inducing a definite hysteresis loop. The slope of P-R variations (using a linear pharmacodynamic model) was greater in the elderly both after IV and single oral verapamil administration, but statistical significance was obtained only after the single oral dose (p<0.05). In the elderly group, after long-term oral administration, there was a significant prolongation of the P-R interval (p<0.0001) with respect to the corresponding time point of the 24-hour predrug period. Such variations in pharmacodynamic parameters in the elderly did not, however, cause any clinical problem.

In conclusion, verapamil seems to be well tolerated in the elderly as well as in younger patients at similar dosages. However, its use in the elderly requires careful clinical evaluation.

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References

  1. Anderson P, Bondesson U, de Faire U. Pharmacokinetics of verapamil in patients with hypertension.Eur J Clin Pharmacol 1986;31:155–163.

    PubMed  Google Scholar 

  2. Ellrodt G, Chew CYC, Singh BN. Therapeutic implications of slow-channel blockade in cardiocirculatory disorders.Circulation 1980;62:669–679.

    PubMed  Google Scholar 

  3. Nissinen A, Koistinen A, Tuomilehto J, et al. Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study.Eur J Clin Pharmacol 1986;31:255–259.

    PubMed  Google Scholar 

  4. Storstein L, Larsen A, Mitbo K, et al. Pharmacokinetics of calcium blockers in patients with renal insufficiency and in geriatric patients.Acta Medica Scand 1984;681 (Suppl.):25–28.

    Google Scholar 

  5. Abernethy DR, Schwartz JB, Todd EL, et al. Verapamil pharmacodynamics and disposition in young and elderly hypertensive patients.Ann Int Med 1986;105:329–336.

    PubMed  Google Scholar 

  6. McAllister RG, Kirsten EB. The pharmacology of verapamil. IV. Kinetic and dynamic effects after single intravenous and oral doses.Clin Pharmacol Ther 1982;31:418–426.

    PubMed  Google Scholar 

  7. Eichelbaum M, Birkel P, Grube E, et al. Effects of verapamil on P-R intervals in relation to verapamil plasma levels following single i.v. and oral administration and during chronic treatment.Klin Wochenschr 1980;58:919–925.

    PubMed  Google Scholar 

  8. Koike Y, Shimamura K, Shudo I, et al. Pharmacokinetics of verapamil in man.Res Comm Chem Pathol Pharmacol 1979;24:37–47.

    Google Scholar 

  9. Reiter MJ, Shand DG, Pritchett ELC. Comparison of intravenous and oral verapamil dosing.Clin Pharmacol Ther 1982;32:711–720.

    PubMed  Google Scholar 

  10. Cinca J, Moya A, Figueras J, et al. Circadian variation in the electrical properties of the human heart assessed by sequential bedside electrophysiologic testing.Am Heart J 1986;112:315–321.

    PubMed  Google Scholar 

  11. Carosella L, Valdina P, Taddei I, et al. Farmacocinetica e farmacodinamica del verapamil nell'anziano.G. Gerontol 1987;35:77–87.

    Google Scholar 

  12. Das DN, Fleg JL, Lakatta EG. Effect of age on the components of atrioventricular conduction in normal man.Am J Cardiol 1982;49:1031.

    Google Scholar 

  13. Bachman S, Sparrow D, Smith LK. Effect of aging on the electrocardiogram.Am J Cardiol 1981;48:513–516.

    PubMed  Google Scholar 

  14. Simonson E. The effect of age on the electrocardiogram.Am J Cardiol 1972;29:64–73.

    Google Scholar 

  15. Padrini R, Barbieri E, Piovan D, et al. Plasma levels and myocardial content of verapamil, norverapamil and two N-dealkyl-metabolites in man.Eur J Clin Pharmacol 1985;28:653–657.

    PubMed  Google Scholar 

  16. Bartels H, Bohmer M, Heierli C. Serum kreatinibestimmung ohne enteiweissen.Clin Chim Acta 1972;37:193–197.

    PubMed  Google Scholar 

  17. Levy G, Gibaldi M. Pharmacokinetics. In: Gillette JR, Mitchell JR (eds.)Handbook of Experimental Pharmacology, New Series: Concepts in Biochemical Pharmacology, Vol. 28 Berlin: Springer Verlag, 1975:18–20.

    Google Scholar 

  18. Wagner JG. Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data.J Pharmacokinet Biopharm 1976;4:443–467.

    PubMed  Google Scholar 

  19. Wagner JG (ed).Fundamentals of Clinical Pharmacokinetics. Hamilton, IL: Drug Intelligence Publications, 1975.

    Google Scholar 

  20. Lown B, Wolf M. Approaches to sudden death from coronary heart disease.Circulation 1971;44:130–142.

    PubMed  Google Scholar 

  21. Holford NHG. Sheiner LB. Understanding the dose-effect relationship: Clinical application of pharmacokinetic-pharmacodynamic models.Clin Pharmacokin 1981;6:429–453.

    Google Scholar 

  22. Greenblatt DJ, Abernathy DR, Shader RI. Pharmacokinetic aspects of drug therapy in the elderly.Ther Drug Monit 1986;8:249–255.

    PubMed  Google Scholar 

  23. Herd JA, Wood AJJ, Blumenthal J, et al. Medical therapy in the elderly.J Am Coll Cardiol 1987;10:29A-34A.

    PubMed  Google Scholar 

  24. Forbes GB, Reina JC. Adult lean body mass declines with age: Some longitudinal observations.Metabolism 1970;19:653–663.

    PubMed  Google Scholar 

  25. Borkan GA, Hults EE, Gerzof AF, et al. Age changes in body composition revealed by computed tomography.J Gerontol 1983;38:673–677.

    PubMed  Google Scholar 

  26. Sheperd AMM, Hewick DS, Moreland TA, et al. Age as a determinant of sensitivity to warfarin.Br J Clin Pharmacol 1977;4:315–320.

    PubMed  Google Scholar 

  27. Hotraphinyo K, Triggs EJ, Maybloom B, et al. Warfarin sodium: Steady-state plasma levels and patient age.Clin Exp Pharmacol Physiol 1978;5:143–149.

    PubMed  Google Scholar 

  28. MacLeod SM, Giles HG, Bengert B, et al. Age- and genderrelated differences in diazepam pharmacokinetics.J Clin Pharmacol 1979;19:15–19.

    PubMed  Google Scholar 

  29. Ewy GA, Kapadia GG, Yao L, et al. Digoxin metabolism in the elderly.Circulation 1969;39:449–453.

    PubMed  Google Scholar 

  30. Cusack B, Kelly J, O'Malley K, et al. Digoxin in the elderly: Pharmacokinetic consequences of old age.Clin Pharmacol Ther 1979;25:772–776.

    PubMed  Google Scholar 

  31. Escher JE, Puthie EH, Gambert SR. Anticoagulants and the elderly: A research dilemma.Age 1986;9:85–90.

    Google Scholar 

  32. Schomerus M, Spiegelhalder B, Stieren B, et al. Physiological disposition of verapamil in man.Cardiovasc Res 1976;10:605–612.

    PubMed  Google Scholar 

  33. Johnston A, Burgess CD, Hamer J. Systemic availability of oral verapamil and effect on PR interval in man.Br J Clin Pharmacol 1981;12:397–400.

    PubMed  Google Scholar 

  34. Anderson P, Bondesson U, Sylven C. Clinical pharmacokinetics of verapamil in patients with atrial fibrillation.Eur J Clin Pharmacol 1982;23:49–57.

    PubMed  Google Scholar 

  35. Dominic JA, Bourne DWA, Tan TG, et al. The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration.J Cardiovasc Pharmacol 1981;3:25–38.

    PubMed  Google Scholar 

  36. Breimer DD. Interindividual variations in drug disposition. Clinical implications and methods of investigation.Clin Pharmacokinet 1983;8:371–377.

    PubMed  Google Scholar 

  37. Young FE. Clinical evaluation of medicines used by the elderly.Clin Pharmacol Ther 1987;42:666–669.

    PubMed  Google Scholar 

  38. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS).N Engl J Med 1987;316:1429–1435.

    Google Scholar 

  39. Cohn Jn, Archibald DG, Ziesche S et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of Veteran Administration Cooperative Study.N Engl J Med 1986;314:1547–1552.

    PubMed  Google Scholar 

  40. Captopril Multicenter Research Group. A placebo controlled trial of captopril in refractory chronic congestive heart failure. J Am Coll Cardiol 1983;2:755–63.

    Google Scholar 

  41. Carbonin PU, Antonelli Incalzi R, Bernabei R. Clinical pharmacology and geriatrics.Lancet 1987;1:747.

    Google Scholar 

  42. Tognoni G, Bonati M. Second-generation clinical pharmacology.Lancet 1986; 2:1028–1029.

    PubMed  Google Scholar 

  43. Zimmer AW, Calkins E, Hadley E, et al. Conducting clinical research in geriatric populations.Ann Intern Med 1985;103:276–283.

    PubMed  Google Scholar 

  44. Baksaas I, Lunde PKM. National drug policies: Needs for drug utilization studies.Trends Pharmacol Sci 1986;7:331–334.

    Google Scholar 

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Authors and Affiliations

  1. Divisione di Gerontologia, Istituto di Clinica Medica, Universita Cattolica del Sacro Cuore, Via Pineta Sacchetti 568, 00168, Rome, Italy

    L. Carosella M.D., P. Menichelli, M. Alimenti, G. Zuccala, A. Gemma, A. Cocchi & P. U. Carbonin

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  1. L. Carosella M.D.
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  2. P. Menichelli
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  3. M. Alimenti
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  4. G. Zuccala
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  5. A. Gemma
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  6. A. Cocchi
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  7. P. U. Carbonin
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Carosella, L., Menichelli, P., Alimenti, M. et al. Verapamil disposition and cardiovascular effects in elderly patients after single intravenous and oral doses. Cardiovasc Drug Ther 3, 417–425 (1989). https://doi.org/10.1007/BF01858113

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