Summary
A metabolite of prazosin was detected in serum from hypertensive patients treated with prazosin. Its structure as 2-(1-piperazinyl)-4-amino-6,7-dimethoxyquinazoline was established by UV, IR, and mass-spectrometry. An assay method for simultaneous determination of prazosin and its metabolite in serum, urine and saliva is described. Preliminary data about the kinetics of prazosin and the metabolite after a single oral dose of prazosin 1 mg, and after multiple doses of 1 to 5 mg t.i.d. for 6–82 days in 7 patients with hypertension, are presented. After the single dose the metabolite level was much lower than that of intact drug, even though the former was eliminated much more slowly than the latter. The slow elimination of the metabolite led to its eventual accumulation in serum during multiple administration. The mean accumulation ratio of the metabolite was estimated to be at least 5.5 (from 3.0 to 7.9). Prazosin itself had a low accumulation ratio, so the mean steady-state level of the intact drug on multiple administration was several times lower than that of metabolite. As this metabolite has some hypotensive effect in animals, it may account for part of the therapeutic activity of parzosin in patients. The mean steady-state concentration of intact prazosin during the course of treatment were found to be significantly lower than that predicted from a single dose study.
Similar content being viewed by others
References
Brogden RN, Heel RC, Speight TM, Avery CS (1977) Prazosin: a review of its pharmacological properties and therapeutic efficacy in hypertension. Drugs 14: 163–197
Bateman DH, Hobbs DC, Twomey TM, Stevens EA, Rawlins MD (1979) Prazosin, pharmacokinetics and concentration effects. Eur J Clin Pharmacol 16: 177–181
Collins JS, Peak P (1975) Pharmcokinetics of prazosin, a new antihypertensive compound. Clin Exp Pharmacol Physiol 2: 445–446
Hobbs DC, Twomey TM, Palmer RF (1978) Pharmacokinetics of prazosin in man. J Clin Pharmacol 18: 402–406
Wood AJ, Simpson FO (1976) Prazosin in normal subjects: plasma levels, blood pressure and heart rate. Br J Clin Pharmacol 3: 199–201
Flouvat B, Le Roux E, Safar M (1978) Pharmacokinetic study of prazosin in man. Excerpta Medica International Congress Series no. 475 Amsterdam. Excerpta Medica 445–446
Grahnen A, Seideman P. Lindström B, Haglund K, von Bahr C (1981) Prazosin kinetics in hypertension. Clin Pharmacol Ther 30: 440–446
Lowenthal DT, Hobbs D, Affrime MB, Twomey TM, Martinez EW, Onesti G (1980) Prazosin kinetics and effectiveness in renal failure. Clin Pharmacol Ther 27: 779–783
Piotrovskii VK, Belolipetskaya VG, El'man AR, Metelitsa VI (1983) Ion-exchange high performance liquid chromatography in drug assay in biological fluids. III. Propranolol, nadolol, prazosin. J Chromatogr 278: 469–474
Taylor JA, Twomey TM, Schach von Wittenau M (1977) The metabolic fate of prazosin. Xenobiotica 7: 357–364
Lin ET, Baughman RA, Benet LZ (1980) High-performance liquid chromatographic determination of prazosin in human plasma, whole blood and urine. J Chromatogr 183: 367–371
Kates RE, Harrison DC, Winkle RA (1982) Metabolite cumulation during long-term oral encainide administration. Clin Pharmacol Ther 31: 427–432
Kates RE, Keefe DL, Winkle RA (1983) Lorcainide disposition kinetics in arrhithmia patients. Clin Pharmacol Ther 33: 28–34
Althuis TH, Hess H-J (1977) Syntheses and identification of the major metabolites of prazosin formed in dog and rat. J Med Chem 20: 146–149
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Piotrovskii, V.K., Veiko, N.N., Ryabokon, O.S. et al. Identification of a prazosin metabolite and some preliminary data on its kinetics in hypertensive patients. Eur J Clin Pharmacol 27, 275–280 (1984). https://doi.org/10.1007/BF00542159
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00542159