European Journal of Clinical Pharmacology

, Volume 39, Issue 4, pp 327–332 | Cite as

The effect of perindopril and hydrochlorothiazide alone and in combination on blood pressure and on the renin-angiotensin system in hypertensive subjects

  • C. L. Brown
  • C. I. Backhouse
  • J. C. Grippat
  • J. Ph. Santoni
Originals

Summary

The pharmacodynamic effects and acceptability of perindopril (4 mg daily) and hydrochlorothiazide (25 mg daily) given alone or in combination for 1 month were investigated in a double-blind, placebo controlled, parallel group study. The pharmacokinetics of perindopril and its active metabolite perindoprilat and the time course of angiotensin converting enzyme inhibition were studied for 72 h following the last dose of treatment in the two appropriate groups.

Similar decreases in blood pressure were seen 24 h after the last dose of perindopril or hydrochlorothiazide (11/7 mm Hg supine) given alone at these doses. The effect of these drugs given together was additive on diastolic blood pressure and synergistic on systolic blood pressure (24.5/12.6 mm Hg supine) taking into account the placebo response. The significant increase in plasma renin activity produced by perindopril alone was potentiated by concurrent administration of hydrochlorothiazide.

The formation of perindoprilat was slightly reduced in the group also receiving hydrochlorothiazide and there was a very small reduction in ACE inhibition in this group.

Perindopril, whether given alone or in combination with hydrochlorothiazide, was well tolerated and produced no clinically significant change in routine haematology or serum biochemistry.

The additive or synergistic effects of perindopril and hydrochlorothiazide on blood pressure must be due to their complementary physiological actions and not to a pharmacokinetic interaction.

Key words

Hypertension perindopril hydrochlorothiazide ACE inhibition pharmacokinetics 

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References

  1. Abrams WB, Davies RO and Gomez HJ (1984) Clinical Pharmacology of enalapril. J Hypertens 2 [Suppl 2]: 31–36Google Scholar
  2. Bussien JP, Fasannela D'amore T, Perret L, Porchet M, Nussberger J, Waeber B and Brunner HR (1986) Single and repeated dosing the converting enzyme inhibitor perindopril to normal subjects. Clin Pharmacol Ther 39: 554–558Google Scholar
  3. Doucet L, De Veyrac B, Delaage M, Cailla H, Bernheim C and Devissaguet M (1990) Radioimmunoassay of a new angiotensin converting enzyme inhibitor (perindopril) in human plasma and urine. Advantages of chromatographic-radioimmunoassay coupling. J Pharm Sci 79: 741–745Google Scholar
  4. Enalapril in Hypertension Study Group (UK) (1984) Enalapril in essential hypertension: a comparative study with propranolol. Br J Clin Pharmacol 198: 51–56Google Scholar
  5. Francis RJ (1984) ELSMOS — an extended least squares modelling system in FORTRAN IV for micro-computer implementations. Comput Prog Biomed 18: 43–50Google Scholar
  6. Hodsman GP, Isles CG, Murray GD, Usherwood TP, Webb DJ and Robertson JIS (1983) Factors related to first dose hypotensive effect of captopril: prediction and treatment. Br Med J 286: 832–834Google Scholar
  7. Joint National Committee on detection, evaluation and treatment of high blood pressure (1988). The 1988 Report. Arch Intern Med 148: 1023–1038Google Scholar
  8. Laubie M, Schiavi P, Vincent M and Schmitt H (1984) Inhibition of angiotensin I converting enzyme with S9490: biochemical effects, interspecies differences and the role of sodium diet in haemodynamic effects. J Cardiovasc Pharmacol 6: 1076–1082Google Scholar
  9. Lees KR and Reid JL (1987) Haemodynamic and humoral effects of oral perindopril, an angiotensin converting enzyme inhibitor, in man. Br J Clin Pharmacol 23: 159–164Google Scholar
  10. Lees KR and Reid JL (1987a) The haemodynamic and humoral effects of treatment for one month with angiotensin converting enzyme inhibitor perindopril in salt replete hypertensive patients. Eur J Clin Pharmacol 31: 519–524Google Scholar
  11. Lees KR, Reid JL, Scott M, Hosie J, Herpin D and Santoni JPH (1989) Captopril versus Perindopril. A double blind study in essential hypertension. J Hum Hypertens 3: 17–22Google Scholar
  12. Luccioni R, Frances Y, Gass R, Schwab C, Santoni JP and Perret L (1988) Evaluation of the dose-effect relationship of a new ACE inhibitor (perindopril) by an automatic blood pressure recorder. Eur Heart J 9: 1131–1136Google Scholar
  13. Ryan JW, Chung A, Ammons C and Carlton ML (1977) A simple radio assay for angiotensin converting enzyme. Biochemistry 167: 501–504Google Scholar
  14. Shepherd AN, Campbell BC and Reid JL (1982) Effects of captopril, an angiotensin converting enzyme inhibitor in normotensive sodium replete volunteers. J Cardiovasc Pharmacol 4: 381–387Google Scholar
  15. Thurston H, Mimran A, Zanchetti A, Creytens G, Rorive G, Brown CL and Santoni JPh (1990) A double-blind comparison of perindopril and atenolol in essential hypertension. J Hum Hypertension 4: (in press)Google Scholar
  16. Webster J, Petrie JC, Robb OJ, Trafford J, Burgess J, Richardson PJ, Davidson C, Fairhurst G, Vandenburg MJ, Cooper WD, Arr SM and Kimber G (1986) Enalapril in moderate to severe hypertension: a comparison with atenolol. Br J Clin Pharmacol 21: 489–495Google Scholar
  17. Webster J, Newnham D, Robb OJ and Petrie JC (1987) Antihypertensive effect of single doses of enalapril in hypertensive patients treated with bendrofluazide. Br J Clin Pharmacol 23: 151–157Google Scholar
  18. Weinberger MH (1982) Comparison of captopril and hydrochlorothiazide alone and in combination in mild to moderate essential hypertension. Br J Clin Pharmacol 14: 127S-131SGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • C. L. Brown
    • 1
  • C. I. Backhouse
    • 2
  • J. C. Grippat
    • 3
  • J. Ph. Santoni
    • 4
  1. 1.Servier Research and DevelopmentFulmerUK
  2. 2.The Medical CentreEast HorsleyUK
  3. 3.Pragmapharm InternationalParisFrance
  4. 4.I.R.I.S.Neuilly-sur-SeineFrance

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