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. 1983 Jun;15(6):719–725. doi: 10.1111/j.1365-2125.1983.tb01556.x

Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man.

J Vincent, H L Elliott, P A Meredith, J L Reid
PMCID: PMC1427926  PMID: 6135439

Abstract

The effects of single doses of doxazosin, a quinazoline derivative similar to prazosin, were studied in six normotensive volunteers. Both 1 mg (i.v.) or 2 mg (oral) doxazosin caused a fall in blood pressure which was most apparent in the erect posture at 5-6 h following drug administration. The maximum fall in blood pressure following i.v. doxazosin was from 123/81 to 106/69 mm Hg associated with a rise in heart rate from 81 to 107 beats/min. The terminal elimination half-life following oral and intravenous doxazosin was about 9 h. Pressor responsiveness to the alpha 1-adrenoceptor agonist, phenylephrine, showed no significant difference between oral and i.v. doxazosin suggesting that the route of administration did not influence alpha 1-adrenoceptor antagonism at the doses used. Using a pharmacodynamic modelling technique in individual subjects, there was a significant correlation between the change in doxazosin concentration in the effect compartment and its hypotensive effect. With the modelling technique it was possible to show a significant correlation between the pressor responsiveness to the alpha 1-adrenoceptor agonist phenylephrine and the concentration of doxazosin in the effect compartment. This is consistent with the concept that the hypotensive effect of doxazosin is mediated by alpha 1-adrenoceptor blockade.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ali F. K., Kossen S. P., Timmermans P. B., Van Zwieten P. A. Effects of prazosin and two of its derivatives (UK 18.596 and UK 33.274) on alpha-adrenoceptors [proceedings]. Br J Pharmacol. 1980 Jan;68(1):113P–113P. [PMC free article] [PubMed] [Google Scholar]
  2. Bateman D. N., Hobbs D. C., Twomey T. M., Stevens E. A., Rawlins M. D. Prazosin, pharmacokinetics and concentration effect. Eur J Clin Pharmacol. 1979 Sep;16(3):177–181. doi: 10.1007/BF00562058. [DOI] [PubMed] [Google Scholar]
  3. Elliott H. L., McLean K., Sumner D. J., Meredith P. A., Reid J. L. Immediate cardiovascular responses to oral prazosin--effects of concurrent beta-blockers. Clin Pharmacol Ther. 1981 Mar;29(3):303–309. doi: 10.1038/clpt.1981.40. [DOI] [PubMed] [Google Scholar]
  4. Elliott H. L., Meredith P. A., Sumner D. J., McLean K., Reid J. L. A pharmacodynamic and pharmacokinetic assessment of a new alpha-adrenoceptor antagonist, doxazosin (UK33274) in normotensive subjects. Br J Clin Pharmacol. 1982 May;13(5):699–703. doi: 10.1111/j.1365-2125.1982.tb01439.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Galeazzi R. L., Benet L. Z., Sheiner L. B. Relationship between the pharmacokinetics and pharmacodynamics of procainamide. Clin Pharmacol Ther. 1976 Sep;20(3):278–289. doi: 10.1002/cpt1976203278. [DOI] [PubMed] [Google Scholar]
  6. Larochelle P., du Souich P., Hamet P., Larocque P., Armstrong J. Prazosin plasma concentration and blood pressure reduction. Hypertension. 1982 Jan-Feb;4(1):93–101. doi: 10.1161/01.hyp.4.1.93. [DOI] [PubMed] [Google Scholar]
  7. Rubin P. C., Brunton J., Meredith P. Determination of the vasodilator UK33274 by high-performance liquid chromatography using fluorescence detection. J Chromatogr. 1980 Nov 14;221(1):193–195. doi: 10.1016/s0378-4347(00)81025-7. [DOI] [PubMed] [Google Scholar]
  8. Seideman P., Grahnén A., Haglund K., Lindström B., von Bahr C. Prazosin dynamics in hypertension: relationship to plasma concentration. Clin Pharmacol Ther. 1981 Oct;30(4):447–454. doi: 10.1038/clpt.1981.187. [DOI] [PubMed] [Google Scholar]
  9. Sheiner L. B., Stanski D. R., Vozeh S., Miller R. D., Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther. 1979 Mar;25(3):358–371. doi: 10.1002/cpt1979253358. [DOI] [PubMed] [Google Scholar]
  10. Sumner D. J., Elliott H. L., Reid J. L. Analysis of the pressor dose response. Clin Pharmacol Ther. 1982 Oct;32(4):450–458. doi: 10.1038/clpt.1982.188. [DOI] [PubMed] [Google Scholar]
  11. Timmermans P. B., Kwa H. Y., Ali F. K., van Zwieten P. A. Prazosin and its analogues UK-18,596 and UK-33,274: a comparative study on cardiovascular effects and alpha-adrenoceptor blocking activities. Arch Int Pharmacodyn Ther. 1980 Jun;245(2):218–235. [PubMed] [Google Scholar]
  12. Whiting B., Kelman A. W. The modelling of drug response. Clin Sci (Lond) 1980 Nov;59(5):311–315. doi: 10.1042/cs0590311. [DOI] [PubMed] [Google Scholar]

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