Summary
The role of acetylator phenotype in determining the response to hydralazine when it was added to diuretic and β-blocker at doses not exceeding 200 mg daily was examined in 57 hypertensive patients. 81% of rapid acetylators needed 200 mg hydralazine daily compared to 38% of slow acetylators (p<0.01). Despite higher doses of hydralazine the blood pressure was controlled in only 27% of rapid acetylators compared to 65% of slow acetylators (p<0.02). The relation of acetylator phenotype to blood pressure response was statistically independent of initial blood pressure, age, sex, body weight and serum creatinine (p<0.005). Current recommendations on hydralazine dosage are unsatisfactory for the 40% of hypertensive patients who are rapid acetylators. We suggest measurement of the acetylator phenotype in patients who respond incompletely to 200 mg hydralazine daily. About 70% of these patients will be rapid acetylators in whom the dose of hydralazine can be increased safely.
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References
Ramsay LE (1980) Diuretic and β-blocker in hypertension — then what? J R Coll Physicians Lond 14: 249–253
Ludden TM, McNay JL, Shepherd AMM, Lin MS (1982) Clinical pharmacokinetics of hydralazine. Clin Pharmacokinet 7: 185–205
Zacest R, Koch-Weser J (1972) Relation of hydralazine plasma concentration to dosage and hypotensive action. Clin Pharmacol Ther 13: 420–425
Silas JH, Ramsay LE, Freestone S (1982) Hydralazine once daily in hypertension. Br Med J 284: 1602–1604
Hunyor SN (1975) Hydralazine and β-blocker in refractory hypertension with characterization of acetylator phenotype. Aust NZ J Med 5: 530–536
Vandenburg MJ, Wright P, Holmes J, Rogers HJ, Ahmad RA (1982) The hypotensive response to hydralazine, in triple therapy, is not related to acetylator phenotype. Br J Clin Pharmacol 1982; 13: 747–750
Kalowski S, Hua ASP, Whitworth JA, Kincaid-Smith P (1979) Hydralazine with beta-blockade and diuretic in the treatment of hypertension. Med J Aust 12: 439–440
Bing RF, Russel GI, Thurston H, Swales JD (1980) Hydralazine in hypertension: is there a safe dose? Br Med J 281: 353–4
Winchester JF, Ward DM, McKillop JH, Kennedy AC (1976) Hydralazine or phentolamine as adjuncts to beta-adrenoceptor blockade/thiazide therapy in hypertension. Br J Clin Pharmacol 3: 863–7
Wilcox RG, Mitchell JRA (1977) Contribution of atenolol, bendrofluazide and hydralazine to management of severe hypertension. Br Med J 2: 547–50
Vree TB, Hebster YA, Baars AM, Damsona JE, van Derkleijh E (1978) Determination of trimethoprim and sulphamethazole (co-trimoxazole) in body fluids by means of high performance liquid chromatography. J Chromatogr 146: 103–12
Baker, RJ, Nelder JA (1978) The GLIM system. Generalised Linear Interactive Modelling Manual. NAG Oxford
Perry HM (1973) Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am J Med 54: 58–72
Ramsay LE (1982) Hypertension. In: Wilkes E (ed) Long-term prescribing. Faber and Faber, London, pp. 18–38
McAreavey D, Ramsay LE, Latham L, Lorimer AR, McLaren D, Reid JL, Robertson JIS, Robertson MP, Weir RJ The “third drug” trial: a comparative study of antihypertensive agents added to treatment when blood pressure is uncontrolled by a beta-blocker plus thiazide diuretic. Br Med J (in press)
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Ramsay, L.E., Silas, J.H., Ollerenshaw, J.D. et al. Should the acetylator phenotype be determined when prescribing hydralazine for hypertension?. Eur J Clin Pharmacol 26, 39–42 (1984). https://doi.org/10.1007/BF00546706
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DOI: https://doi.org/10.1007/BF00546706