Conjugative metabolites, biological activity

Metabolism leads to their rapid deactivation in tire body and, hence, these compounds exhibit little oral activity. Thus, they have to be given parenterally. Most of the catabolism of these compounds occurs in liver, and enterohepatic circulation may then occur, with the metabolites exerting little if any biological activity. In cattle, most of these compounds are eliminated in feces where 60-90% of the metabolites are found in the free form. In conttast, metabolites occurring in urine are predominantly in conjugated forms. 

Table 8.1 Biological Activities of Conjugated Quercetin Metabolites...

Some of these oxidative metabolites are biologically active and may even be more toxic than their parent compounds. Conversion by conjugation reactions is considered to lead to termination of the toxicity of these compounds and excretion of the non-toxic conjugates.58 Oxidative metabolism of a parent compound can lead to different products which may be excreted at different rates, as has been demonstrated for hydroxylated benzo[a]pyrenes.58... 

Verapamil is a synthetic compound possessing slight structural similarity to papaverine. It can be separated into its optically active isomers, of which the levorotatory enantiomer is the most potent. It is absorbed rapidly after oral administration. The drug is metaboli zed quickly and. as a result, has low bioavailability. The liver is the main site of first-pass metaboli.sm. forming several products. The preferential metabolic step involves N-dealkylation. followed by O-demethylation. and subsequent conjugation of the product before elimination. The metabolites have no significant biological activity. Verapamil has an elimination half-life of approximately 5 hours. 

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