Drug action biological half life

Mechanism of Action. The drug is usually absorbed by the oral route upto 90-100%. However, its absorption is predominantly diminished to a small extent milk and food intake and appreciably by the presence of iron preparations and nonsystemic antacids . It is protein-bound in plasma between a range of 70-75%. The volume of distribution v/ stands at 0.14 - 0.7 mL. The plasma half-life ranges between 11-17 hours. It gets excreted unchanged in urine upto 10% however, its biological half-life is usually prolonged chiefly in the incidence of renal failure. 

Okita [107] has studied the difference in duration of action of digoxin in various species. He found that biological half-life was directly related to the duration of drug action and concluded that half-life is a measure of the relative duration of action of pharmacological agents. These data are related to the LDgo for the various species and are summarized in Table 9. 

Most species differences in drug metabolism, however, result from differences in the rates of enzymatic convosions. For example, a dose of 50 mg/kg of hexo-barbital produces anaesthesia in man or dog for over S hr but 100 mg/kg produces anaesthesia for 90 min in rats, for 49 min in rabbits and for only 12 min in mice. At the time of recovery from anaesthesia, the several animal spedes have remarkably similar brain barbiturate levels. Thus, the duration of action of hexo-barbital in several species is generally proportional to its biologic half life and inversely proportional to the rate of hexobarbital metabolism by enzymes in hepatic microsomes. 

The duration of action and the biological half-life of many drugs are considerably shorter in male rats than in female rats. These differences are inversely related to the activity of microsomal enzymes and are under the control of sex hormones. For example, female rats have relatively prolonged hexobarbital sleeping times and low microsomal enzyme activity whereas males have short sleeping times and relatively high enzyme activity (Table 11). Administration of testosterone to... 

In addition to the slow onset of action of amiodarone, the half-life of the biological effects of the drug are extremely long [30]. This may be due in part to the principal metabolite of (11), which is desethylamiodarone (18). 

Besides pharmacon metabolism, pharmacon transport is a major factor in determining the bioavailability profile and hence the biological action of pharmaca. Thus, modulation of drug transport by molecular manipulation also offers opportunities to modify the action profile, e.g. the half-life of bioactive compounds. 

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