Metabolite kinetics

The enterohepatic circulation may sometimes prolong the half-life of a drug. A drug that is absorbed from the gastrointestinal tract, excreted in the bile, and resorbed from the intestine is said 

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Safety evaluations involving preformed or synthetic metabolitefs) of a drug should take metabolite kinetics into considerations. 

Pmeksaritanont, T., Lin, J. H. et al. (2006). Complicating factors in safety testing of drag metabolites Kinetic differences between generated and preformed metabolites. Toxicol. Appl. Pharmacol. 217(2) 143-152. 

Houston J. Drug metabolite kinetics. Pharmacol Ther 1982 15 521-552. 

Whereas the radioactivity measurement alone does not allow distinguishing between drug and metabo-lite(s), samples obtained from the described studies should be also used for standard determination of the drug and its known metabolites, receiving information about the drag and the known metabolite kinetics directly. The gap between radioactivity concentrations and the concentrations determined by direct bioana-lytical methods defines the contribution of unknown metabolites. 

The clearance concept can successfully be applied to analyze metabolite kinetics in blood (13). It can, by analogy, be used for the kinetics of the active moiety after prodrug administration. As with the compartmental approach, care must be taken when prodrug transformation occurs during first pass and/or prodrug excretion is important after it reaches the systemic circulation. Here again, some differences with metabolite kinetics occur in the function of two different aspects ... 

Metabolite kinetics of classical drugs are not always studied after their administration to humans, whereas the active moiety of a prodrug should always be well investigated from a pharmacokinetic point of view. This means that the basic pharmacokinetic parameters (ll)are estimated and that they can be used to extract relevant information when the prodrug is administered. 

In light of a high degree of structural variability of drugs, multiplicity of kinetics and metabolite kinetics, the task of establishing a clear correlation between the structured chemistry of substituents and their pharmacokinetic properties appears somewhat daunting. The pharmacokinetic fate of a drug molecule, however, appears to be a consequence of its physicochemical properties and, therefore, may, to some extent, be predicted from its chemical structure. 

We remain cognizant that this edition of the textbook includes some references that may be considered by some viewers not to be the most current. We, however, believe that the chosen references are classic ones best suited to illustrate a particular point. Additionally, we fully recognize that this edition omits topics such as the Wagner and Nelson method for the determination of the absorption rate constant, urinary data analysis following the administration of a drug by an extravascular route, two-compartment model pharmacokinetics for an extravascularly administered dmg, and metabolite kinetics. 

Contin RivaR, Albani F, Baruzzi A. Effect of felbamate on clobazam and its metabolite kinetics in patients with epilepsy. Ther Drug Monit ( 999)2, 604-8. 

Papalexandratou Z, Falony G, Romanens E, Jimenez JC, Amores F, Daniel H-M, De Vuyst L (201 lb) Species diversity, community dynamics, and metabolite kinetics of the microbiota associated with traditional Ecuadraian spontaneous cocoa bean fermentatimis. Appl Environ Microbiol 77 7698-7714... 

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