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Abstract

Excretion and metabolism of recainam, a new anti-arrhythmic drug, in laboratory animals and humans.

J A Scatina, D S Wells, H B Kimmel, C J Kemper and S F Sisenwine
Drug Metabolism and Disposition September 1990, 18 (5) 746-752;
J A Scatina
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D S Wells
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H B Kimmel
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C J Kemper
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S F Sisenwine
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Abstract

The metabolic disposition of recainam, an antiarrhythmic drug, was compared in mice, rats, dogs, rhesus monkeys, and humans. Following oral administration of [14C]recainam-HCl, radioactivity was excreted predominantly in the urine of all species except the rat. Metabolite profiles were determined in excreta by HPLC comparisons with synthetic standards. In rodents and rhesus monkeys, urinary excretion of unchanged recainam accounted for 23-36% of the iv dose and 3-7% of the oral dose. Aside from quantitative differences attributable to presystemic biotransformation, metabolite profiles were qualitatively similar following oral or iv administration to rodents and rhesus monkeys. Recainam was extensively metabolized in all species except humans. In human subjects, 84% of the urinary radioactivity corresponded to parent drug. The major metabolites in mouse and rat urine and rat feces were m- and p-hydroxyrecainam. Desisopropylrecainam and dimethylphenylaminocarboxylamino propionic acid were the predominant metabolites in dog and rhesus monkey urine. Small amounts of desisopropylrecainam and p-hydroxyrecainam were excreted in human urine. Selective enzymatic hydrolysis revealed that the hydroxylated metabolites were conjugated to varying degrees among species. Conjugated metabolites were not present in rat urine or feces, while conjugates were detected in mouse, dog, and monkey urine. Structural confirmation of the dog urinary metabolites was accomplished by mass spectral analysis. The low extent of metabolism of recainam in humans suggests that there will not be wide variations between dose and plasma concentrations.

 

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Drug Metabolism and Disposition
Vol. 18, Issue 5
1 Sep 1990
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Abstract

Excretion and metabolism of recainam, a new anti-arrhythmic drug, in laboratory animals and humans.

J A Scatina, D S Wells, H B Kimmel, C J Kemper and S F Sisenwine
Drug Metabolism and Disposition September 1, 1990, 18 (5) 746-752;

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Abstract

Excretion and metabolism of recainam, a new anti-arrhythmic drug, in laboratory animals and humans.

J A Scatina, D S Wells, H B Kimmel, C J Kemper and S F Sisenwine
Drug Metabolism and Disposition September 1, 1990, 18 (5) 746-752;
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