What tentative conclusions can be drawn concerning the Phase I Functionalisation metabolism of Compound A in the four species? Answer

 
Phase I Functionalisation metabolism of Compound A in all species causes its conversion into a relatively inactive and more polar metabolite by introduction of new polar functional groups. In dog phase-I reaction is enough to make compound A polar for excretion but in man and rat phase-II reaction (sulphate conjugation) is also required to make compound A more polar for excretion. In man and rat aromatic –OH group is generated by aromatic hydroxylation and O-dealkylation respectively. In dog carboxylic polar group generated by oxidative deamination and oxidation of aldehyde group. These metabolites will be successively excreted easily from urine. Every species having different Phase I functionalization reactions for same compound A. So metabolic studies of drug separately in human being are very important. Metabolism of compound A in man is more similar to rat rather than dog.

3. What significance does this knowledge of metabolism have in interpretation of the pharmacokinetic data?
Answer
Knowledge of metabolism is important in interpretation of number of different important pharmacokinetic parameters. Drug and metabolite excretion data can be used to calculate the various pharmacokinetic parameters of drug. Inter species differences in metabolism of a drug is also an important factor for interpretation of pharmacokinetic data. E.g. in some cases, metabolism of a drug lead to formation of more potent therapeutically