Summary
The metabolism of cadralazine I was studied after oral administration to rat. Besides consistent amount of unchanged drug, three metabolites were separated in urine by TLC and GC and their structures elucidated by mass spectrometry in comparison with synthetie samples. A specific and sensitive method was developed to detect the decarbethoxylated metabolite III at nanogram levels.
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Pifferi G., Parravicini F., Scarpitta G. and Semeraro C. (1978): Synthesis and antihypertensive activity of new 6-substituted 3-alkyl- and 3-acyl-hydrazinopyri-dazines. Vlth Int. Symposium on Medicinal Chemistry. Brighton, September 4-7; Abs. P 17.
Parravicini F., Scarpitta G., Dorigotti L. and Pifferi G. (1979): Derivati della 3-idrazinopiridazina. Sintesi ed attività antiipertensiva di nuove 3-(2-acilidrazino)-pyridazine-6-alchilamino sostituite. Farmaco, Ed. Sci.,34, 299–310.
Carpi C, Dorigotti L. and Semeraro C. (1978): Pharmacological profile of a new antihypertensive drug: ethyl 2-[6-[(2-hydroxypropyl)ethylamino]-3-pyridazinyl]hydrazinecarboxylate (ISF 2469) 7th Int. Congress of Pharmacology (IUPHAR). Paris, June 16–21; Abs. 2700.
van Brummelen P., Bühler F.R., Kiowski W., Bolli P. and Bertel O. (1979): Antihypertensive efficacy of a new long acting vasodilator, ISF 2469, in combination with a betablocker and a diuretic. Int. J. Clin. Pharmacol, and Biopharm.,17, 380–385.
Amann F.W. and Bühler F.R. (1979): Long-therm antihypertensive therapy with a new vasodilator, ISF 2469, in combination with a betablocker and a diuretic. Clinica Europea,18, 1028–1034.
Frattini C. (1980): Degradazione della cadralazina in soluzione acquosa. Thesis, Faculty of Pharmacy, University of Milan.
Pifferi G., Parravicini F., Carpi C. and Dorigotti L. (1975): Synthesis and antihypertensive properties of new 3-hydrazinopyridazine derivatives. J. Med. Chem.,18, 741–746.
Smith K.M., Johnson R.N. and Kho B.T. (1977): Determination of hydralazine in tablets by gaschromatography. J. Chromatogr.,137, 431–436.
Budzikiewicz H., Djerassi C., Williams D.H. (1967): In «Mass spectrometry of organic Compounds». Holden Day Inc., San Francisco; pp. 569–570.
Beretta E., Cristina T., Ferrari P., Tuan G., Zerilli L.F. and Martinelli E. (1979): Metabolites of 3-hydrazino-6-[bis-(2-hydroxyethyl)amino]pyridazine dihydro-chloride in rat urine. Eur. J. Drug Metab. Pharmacokinet.,4, 29–33.
Haegele K.D., Skrdlant H.B., Robie N.W. Lalka D. and McNay J.L. (1976): Determination of hydralazine and its metabolites by gaschromatographymass spectrometry. J. Chromatogr.,126, 517–534.
Moroi R., Ono R., Saito T., Akimoto T. and Sano M. (1977): Metabolism of budralazine, a new antihypertensive agent. II. Metabolic pathways of budralazine in rat. Chem. Pharm. Bull.,25, 830–835.
Ishii A., Deguchi J. and Takahira H. (1973): Studies on14C labelled N1-carboethoxy-N2-hydrazinophtalazine hydrochloride (Apiracohl®). I. Synthesis of labelled compound and metabolism in rats. Yakugaku Zasshi,93, 1383–1390.
Simonotti L., Colombo R. and Pifferi G. (1979): Gaschromatographic mass spectrometric identification of urinary metabolites of propildazine in rat. In «Récent developments in mass spectrometry in biochemistry and medicine». Ed. by Frigerio A., Plenum Press, New York and London, pp. 27–41.
Carpi C, Dorigotti L. and Semeraro C. (1980): Cadralazine and its identified metabolites: comparative effects on blood pressure and on arterial smooth muscle. Proceedings of the Joint Meeting of Italian and English Pharmacological Societies, Verona, 30th June-1st July; P. 30.
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Simonotti, L., Zanol, M., Parravicini, F. et al. Studies on the metabolism of cadralazine in rat. European Journal of Drug Metabolism and Pharmacokinetics 7, 39–45 (1982). https://doi.org/10.1007/BF03189541
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DOI: https://doi.org/10.1007/BF03189541