Skip to main content
SpringerLink
Log in

The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin

  • Short Communications
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

In a single-blind study 12 normotensive men took nifedipine 20 mg (Group 1, n=6) or doxazosin 2 mg (Group 2, n=6), followed by the combination. Each subject attended on four 9-h study days for evaluation of the effects of single and multiple doses of the monotherapy and the effects of adding single and multiple doses of the second drug. Measurements of BP, HR, plasma drug concentrations, and apparent liver blood flow were recorded. The combination was generally well tolerated.

BP was consistently lower with the combination than with either monotherapy: for example, average erect BP was 108/61 (Group 1) and 112/62 mmHg (Group 2) compared with 122/66 and 116/68 during steady-state monotherapy.

The introduction of nifedipine in Group 2 was associated with a significant increase in liver blood flow at 1.5 h: 1560 vs 1050 ml · min−1 during monotherapy with doxazosin.

There was no significant kinetic interaction. In particular, the steady-state AUC of doxazosin was unaffected by the addition of nifedipine: 257, 307, 301, and 256 ng · ml−1 · h for the 4 study days (Group 2).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Jee LD, Opie LH (1983) Acute hypotensive response to nifedipine added to prazosin in treatment of hypertension. Br Med J 287: 1514–1515

    Google Scholar 

  2. Pasanisi F, Elliott HL, Meredith PA, McSharry DR, Reid JL (1984) Combined alpha adrenoceptor antagonism and calcium channel blockade in normal subjects. Clin Pharmacol Ther 36: 716–723

    Google Scholar 

  3. Elliott HL, Meredith PA, Campbell L, Reid JL (1988) The combination of prazosin and verapamil in the treatment of essential hypertension. Clin Pharmacol Therap 43: 554–560

    Google Scholar 

  4. Schoors DF, Vercruy I, Musch G, Massart DL, Dupont AG (1990) Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers. Br J Clin Pharmacol 29: 497–501

    Google Scholar 

  5. Elliott HL, Meredith PA, Reid JL (1991) Interactions between nisoldipine and the beta blockers atenolol and propranolol. Br J Clin Pharmacol 32: 379–386

    Google Scholar 

  6. Waller DJ, Renwick AG, Gruchy BS, George CF (1981) The first pass metabolism of nifedipine in man. Br J Clin Pharmacol 18: 1174–1177

    Google Scholar 

  7. Rubin PC, Brunton J, Meredith PA (1980) Determination of the vasodilator UK 33274 by HPLC using fluorescence detection. J Chromatogr 221: 193–195

    Google Scholar 

  8. Caesar J, Shaldon S, Chiandussi L et al (1961) The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 21: 43–57

    Google Scholar 

  9. McKenzie JK, Clements JA (1974) Simplified radioimmunoassay for serum aldosterone utilising increased antibody specificity. J Clin Endocrinol Metab 38: 622–627

    Google Scholar 

  10. Derkx FHM, Boomsma BN, Tan-Tjiong HL, Schalekamp MADH (1980) Role of plasma kallikrein in the proteolytic activation of the renin-angiotensin system. Clin Exp Hypertens 2: 575–592

    Google Scholar 

  11. Da Prada M, Zurcher G (1976) Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range. Life Sci 19: 1161–1174

    Google Scholar 

  12. Sluiter AG, Suysmans STM, Thien TA, Koener LP (1985) The influence of alpha1 adrenergic blockade on the acute antihypertensive effect of nifedipine. Eur J Clin Pharmacol 29: 263–267

    Google Scholar 

  13. Lenz M, Varghese A, Pool J, Laddu A, Johnston W, Piwinski S, Taylor A (1991) Combined terazosin and verapamil therapy in essential hypertension: haemodynamic interactions (Abstract). Clin Pharmacol Ther 49: 146

    Google Scholar 

  14. Varghese A, Lenz M, Locke C, Granneman R, Laddu A, Pool J, Piwinski S, Taylor A (1991) Combined terazosin and verapamil therapy in essential hypertension: pharmacokinetic interactions (Abstract). Clin Pharmacol Therap 49: 130

    Google Scholar 

  15. Donnelly R, Elliott HL, Meredith PA, Howie CA, Reid JL (1992) Combination of nifedipine and doxazosin in essential hypertension. J Cardiovasc Pharmacol 19: 479–486

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University Department of Medicine and Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK

    R. Donnelly, H. L. Elliott, P. A. Meredith, C. A. Howie & J. L. Reid

Authors
  1. R. Donnelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. L. Elliott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. A. Meredith
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. A. Howie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. L. Reid
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donnelly, R., Elliott, H.L., Meredith, P.A. et al. The pharmacodynamics and pharmacokinetics of the combination of nifedipine and doxazosin. Eur J Clin Pharmacol 44, 279–282 (1993). https://doi.org/10.1007/BF00271372

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00271372

Key words

Search

Navigation