Identification of Urinary and Biliary Metabolites of Alprenolol in the Rat

Hoffmann, Kurt‐Jürgen; Arfwidsson, A.; Borg, K. O.; Skånberg, Inger

doi:10.3109/00498257909038710

Cited by 13 publications

(2 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The problems involved in the preparation of TMS derivatives of carbamates have been reported by several authors (18)(19)(20), who emphasize the risk of structural transformations during GLC chromatography. For-the same reason, TMS derivatization of metabolite H 119/84 could not be used for elucidating the actual position of the hydroxy group as reported for the corresponding hydroxylated metabolites of metoprolol (21) and alprenolol (22). The accessibility of the secondary amine in the long sidechain for formation of a TMS derivative strongly o depends upon the reagent used.…”

Section: Analytical Aspectsmentioning

confidence: 99%

“…The accessibility of the secondary amine in the long sidechain for formation of a TMS derivative strongly o depends upon the reagent used. We have previously reported that BSAas a silyl donator did not react with the isopropylamino group (9,21,22) but, depending upon gas-chromatographic and reagent conditions, partial N-TMS formation can occur. With a weak silyl donator, such as hexamethylenedisilazane, this reaction can be avoided,leaving the nitrogen underivatized.…”

Section: Analytical Aspectsmentioning

confidence: 99%

See 1 more Smart Citation

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Hoffmann¹,

Skånberg²,

Borg³

1979

European Journal of Drug Metabolism and Pharmacokinetics

Self Cite

View full text Add to dashboard Cite

The metabolism of pamatolol was studied in man, dogs, rats and mice after oral administration of a single dose. The drug was well absorbed in the gastro-intestinal tract and excreted in the urine, mainly in unchanged form, within 24 hrs. Four urinary metabolites were identified by gas chromatographic-mass spectrometric techniques. The metabolic data, in man, dog and mouse was found to be similar, both qualitatively and quantitatively. One metabolism route, involving aliphatic hydroxylation and subsequent oxidation, was found, to a significant extent only in the rat. The species variation between the mouse and the rat with regard to long-term toxicity of pamatolol is discussed. Artefact formation during trace analysis was observed.

show abstract

Section: Analytical Aspectsmentioning

confidence: 99%

Section: Analytical Aspectsmentioning

confidence: 99%

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Hoffmann¹,

Skånberg²,

Borg³

1979

European Journal of Drug Metabolism and Pharmacokinetics

Self Cite

View full text Add to dashboard Cite

show abstract

Biliary excretion and enterohepatic circulation of two beta‐adrenergic blocking drugs, exaprolol and propranolol in rats

Tomcíková

Bezek

Ďurišová

et al. 1984

Biopharm & Drug Disp

View full text Add to dashboard Cite

Plasma levels and excretion of two beta-adrenoceptor blocking drugs 3H-exaprolol and 3H-propranolol were observed up to 96 h after a single i.v. administration to rats. Terminal half-lives of 26.8 +/- 9.1 h and 51.3 +/- 7.5 h were found for exaprolol and propranolol, respectively. The recovery of 3H radioactivity in feces following i.v. administration of the drugs (34.2 +/- 0.8 per cent and 12.0 +/- 1.3 per cent 3H of exaprolol and propranolol, respectively) is of biliary origin, as 30.7 +/- 3.5 per cent and 13.4 +/- 3.6 per cent 3H of exaprolol and propranolol, respectively, was excreted in the bile after i.v. administration. Enterohepatic circulation of the drugs was studied using the donor-recipient rat method. After intraduodenal administration of donor bile to the recipient rat approximately 50 per cent and 40 per cent of the biliary 3H activity of exaprolol and propranolol, respectively, was re-excreted following absorption. A formula for calculating the amount of the substance together with its metabolites excreted in the bile, urine or feces as a result of enterohepatic circulation has been proposed.

show abstract

Biotransformation of terodiline I. Identification of metabolites in dog urine by mass spectrometry

Norén

Strömberg

Ericsson

et al. 1985

Biol. Mass Spectrom.

View full text Add to dashboard Cite

Nine metabolites of terodiline (N-tert-butyl-4,4-diphenyl-2-butylamine) have been identified in dog urine by various chromatographic techniques and mass spectrometry. The main metabolic pathway is aromatic hydroxylation, leading to the quantitatively most important metabolite, N-tert-butyl-4-(4-hydroxyphenyl)-4-phenyl-2-butylamine, and to two dihydroxylated metabolites, one mono substituted in both rings (N-tert-butyl-4,4'-bis(4-hydroxyphenyl)-2-butylamine), and one disubstituted in one ring (N-tert-butyl-4-(3,4-dihydroxyphenyl)-4-phenyl-2-butylamine). The latter is further metabolized by methylation, forming N-tert-butyl-4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-butylamine, the second most abundant metabolite. Still another metabolite is formed by hydroxylation in the tert-butyl group to N-(2-hydroxymethyl-2-propyl)-4,4-diphenyl-2-butylamine. A very minor dihydroxylated metabolite results from oxidation both in an aromatic ring and in the tert-butyl group, giving N-(2-hydroxymethyl-2-propyl)-4-(4-hydroxyphenyl)-4-phenyl-2-butylamine. Oxidation of the carbon adjacent to the nitrogen and subsequent deamination gives the two ketones 4-(4-hydroxyphenyl)-4-phenyl-2-butanone and 4-(4-hydroxy-3-methoxyphenyl)-4-phenyl-2-butanone. Reduction of the carbonyl function in the former yields the corresponding alcohol, 4-(4-hydroxyphenyl)-4-phenyl-2-butanol. Some unchanged terodiline is also present. All metabolites formed by functionalization appear to be extensively conjugated, presumably with glucuronic acid.

show abstract

Identification of Urinary and Biliary Metabolites of Alprenolol in the Rat

Cited by 13 publications

References 13 publications

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Species differences in the metabolism of pamatolol, a cardioselective beta — adrenoceptor antagonist

Biliary excretion and enterohepatic circulation of two beta‐adrenergic blocking drugs, exaprolol and propranolol in rats

Biotransformation of terodiline I. Identification of metabolites in dog urine by mass spectrometry

Contact Info

Product

Resources

About