Identification of two metabolites of hydralazine from human urine

Zak, Sylvai B.; Gilleran, Thomas G.; Karliner, Jerrold; Lukas, George

doi:10.1021/jm00249a035

Cited by 32 publications

(12 citation statements)

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“…The latter undergoes oxidation to 3-carboxy-s-triazolo[3,4-a]phthalazine (23)64,65 followed by decarboxylation to s-triazolo[3,4-a]phthalazine (14). 66 It appears that hydralazine can undergo hydroxylation prior to acetylation resulting in the formation of 4-hydrazino-l-(W)phthalazinone (24) and 2-acetyl-4-hydrazino-l-(2H)phthalazinone (25). 59 The latter is excreted mainly as conjugates.…”

Section: Metabolismmentioning

confidence: 99%

Hydralazine and related compounds: Chemistry, metabolism, and mode of action

Reece

1981

Medicinal Research Reviews

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Section: Metabolismmentioning

confidence: 99%

Hydralazine and related compounds: Chemistry, metabolism, and mode of action

Reece

1981

Medicinal Research Reviews

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“…The literature contains numerous examples of the in uiuo formation of IIIb, a known major metabolite of hydralazine (8,9), via enzymatic acetylation of hydralazine and subsequent dehydration (Scheme I, Pathway A) (3,4). Hydralazine reaction with formaldehyde and acetaldehyde for 30 min at 37O resulted in the formation of IIIa and IIIb, respectively, which showed strong fluorescence and UV absorption.…”

Section: Resultsmentioning

confidence: 99%

High-Performance Liquid Chromatographic Studies of Reaction of Hydralazine with Biogenic Aldehydes and Ketones

O’Donnell

Proveaux

K.H.

1979

Journal of Pharmaceutical Sciences

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“…The metabolic pathway for formation of Metabolite II goes without doubt by way of acetylation of the hydrazine function (13,14), with possible formation of an intermediate which is probably Metabolite III. It is not yet possible to be sure of the metabolic pathway by which Metabolite I is formed.…”

Section: Discussionmentioning

confidence: 99%

Disposition and metabolism of 3-hydrazino-6-[N,N-bis(2-hydroxyethyl)amino] pyridazine dihydrochloride in man

Assandri

Perazzi

Buniva

et al. 1979

European Journal of Drug Metabolism and Pharmacokinetics

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Three healthy volunteers (two men and one woman) were given single oral doses of 14 mg of 14C-labelled 3-hydrazino-6-[N N-bis(2-hydroxyethyl)amino] pyridazine dihydrochloride, a new anti-hypertensive agent. The drug was absorbed well, and peak levels of i4C-activity in the plasma, reached after 1.5-2.0 hrs, ranged between 98 and 161 ng eq/ml. The plasma half-lives of total radiocarbon calculated from the decline in the concen tration curves between 2 and 8 hrs varied between 1.4 and 2.1 hr. This phase of rapid decline was followed by a second one with a slower rate of disappearance of 14C. Approximately 40% of the radioactivity in the whole blood was confined to the plasma. Within 6 days an average of 102% of the administered dose was recovered, 57% being excreted in the urine and 45% in the faeces. Of the total radioactivity excreted in the urine, more than 70% was eliminated within the first 8 hrs. In the 24-hr urine, the radioactivity due to the two identified metabolites, 3-rbis (2 hydroxyethyljamino1pyridazine and 3-methyl-6-rbis (2-hydroxyethyl)amino] -s-triazole [4,3-b] pyridazine, did not account for more than 28% of the total radioactivity. Moreover, the second metabolite was shown to derive from another one present in the urine in substantial quantity (38%). It cannot be stated with certainty whether or not any unchanged drug was excreted in the urine.

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Identification of two metabolites of hydralazine from human urine

Cited by 32 publications

References 0 publications

Hydralazine and related compounds: Chemistry, metabolism, and mode of action

Hydralazine and related compounds: Chemistry, metabolism, and mode of action

High-Performance Liquid Chromatographic Studies of Reaction of Hydralazine with Biogenic Aldehydes and Ketones

Disposition and metabolism of 3-hydrazino-6-[N,N-bis(2-hydroxyethyl)amino] pyridazine dihydrochloride in man

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