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Drug Metabolism & Disposition

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Abstract

The metabolic disposition of the selective beta 1-adrenoceptor agonist prenalterol in mice, rats, dogs, and humans.

K J Hoffmann, A Arfwidsson and K O Borg
Drug Metabolism and Disposition March 1982, 10 (2) 173-179;
K J Hoffmann
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A Arfwidsson
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K O Borg
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Abstract

The metabolic routes of the selective beta 1-adrenoceptor agonist prenalterol have been studied in mice, rats, dogs, and humans after oral administration. The drug was well absorbed from the gastrointestinal tract and most of the administered radioactivity was excreted in urine from all species within 24 hr. Prenalterol was metabolized to a varying extent in the species studied. About 20% of the 10-mg dose was recovered unchanged in man, the corresponding figures being 1.8% in the mouse, 7% in the rat, and 54% in the dog at 0.263 mg/kg (1 mumol/kg). Three metabolites were characterized and quantified by thin-layer chromatography, high-performance liquid chromatography, nuclear magnetic resonance (1H and 13C), and gas chromatography-mass spectrometry. Pronounced species variations in the metabolic pattern were observed. The phenolic sulfate ester of prenalterol was the main urinary metabolite in man, important in the dog, minor in the rat but not detectable in the mouse. Prenalterol glucuronide was formed in significant amounts in the animals and, in addition, beta-4(hydroxyphenoxy)lactic acid was present in dog urine. In the rat and the mouse the degree of biotransformation of prenalterol was significantly decreased at high oral doses of 2630 mg/kg (10 mmol/kg). The synthesis of prenalterol sulfate ester with use of ion pair extraction techniques is described.

 

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Drug Metabolism and Disposition
Vol. 10, Issue 2
1 Mar 1982
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Abstract

The metabolic disposition of the selective beta 1-adrenoceptor agonist prenalterol in mice, rats, dogs, and humans.

K J Hoffmann, A Arfwidsson and K O Borg
Drug Metabolism and Disposition March 1, 1982, 10 (2) 173-179;

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Abstract

The metabolic disposition of the selective beta 1-adrenoceptor agonist prenalterol in mice, rats, dogs, and humans.

K J Hoffmann, A Arfwidsson and K O Borg
Drug Metabolism and Disposition March 1, 1982, 10 (2) 173-179;
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