Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1978 Jun;5(6):489–494. doi: 10.1111/j.1365-2125.1978.tb01662.x

Identification of hydrallazine and hydrallazine hydrazone metabolites in human body fluids and quantitative in vitro comparisons of their smooth muscle relaxant activity.

K D Haegele, A J McLean, P du Souich, K Barron, J Laquer, J L McNay, O Carrier
PMCID: PMC1429372  PMID: 656292

Abstract

1 Serum and urine from hypertensive subjects on chronic oral hydrallazine therapy were studied using gas chromatographic/mass spectrometry techniques. 2 Metabolites resulting from acetylation, hydrolysis and conjugation reactions were detected. The acetone, pyruvate and alpha-ketoglutarate hydrazone were identified. 3 The activity of the pyruvate and alpha-ketoglutarate hydrazones were compared with that of hydrallazine using isolated rabbit aortic strips. 4 Both hydrazones were active under in vitro conditions, producing smooth muscle relaxant effects equal to those of hydrallazine. 5 It is concluded that hydrazone metabolites will contribute to the hypotensive effects of hydrallazine therapy in proportion to their relative abundance, persistence in vascular tissues and intrinsic activity.

Full text

PDF
489

Selected References

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

  1. Barron K., Carrier O., Haegele K. D., McLean A. J., McNay J. L., Du Souich P. Comparative evaluation of the in vitro effects of hydralazine and hydralazine acetonide on arterial smooth muscle. Br J Pharmacol. 1977 Nov;61(3):345–349. doi: 10.1111/j.1476-5381.1977.tb08426.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. DRUEY J., MARXER A. Hypotensive hydrazinophthalazines and related compounds. J Med Pharm Chem. 1959 Feb;1(1):1–21. doi: 10.1021/jm50002a001. [DOI] [PubMed] [Google Scholar]
  3. Haegele K. D., Skrdlant H. B., Robie N. W., Lalka D., McNay J. L., Jr Determination of hydralazine and its metabolites by gas chromatography-mass spectrometry. J Chromatogr. 1976 Nov 3;126:517–534. doi: 10.1016/s0021-9673(01)84098-x. [DOI] [PubMed] [Google Scholar]
  4. MCISAAC W. M., KANDA M. THE METABOLISM OF 1-HYDRAZINOPHTHALAZINE. J Pharmacol Exp Ther. 1964 Jan;143:7–13. [PubMed] [Google Scholar]
  5. Perry H. M., Jr Late toxicity to hydralazine resembling systemic lupus erythematosus or rheumatoid arthritis. Am J Med. 1973 Jan;54(1):58–72. doi: 10.1016/0002-9343(73)90084-3. [DOI] [PubMed] [Google Scholar]
  6. SCHULERT A. R. Physiological disposition of hydralazine (1-hydrazinophthalazine) and a method for its determination in biological fluids. Arch Int Pharmacodyn Ther. 1961 Jun 1;132:1–15. [PubMed] [Google Scholar]
  7. Talseth T. Studies on hydralazine. II. Elimination rate and steady-state concentration in patients with impaired renal function. Eur J Clin Pharmacol. 1976 Sep 30;10(5):311–317. doi: 10.1007/BF00565619. [DOI] [PubMed] [Google Scholar]
  8. Zak S. B., Lukas G., Gilleran T. G. Plasma levels of real and "apparent" hydralazine in man and rat. Drug Metab Dispos. 1977 Mar-Apr;5(2):116–121. [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES