Irodalmi osszefoglalo Overview of hepatic cytochrome P450 enzymes involved in human, dog and porcine xenobiotic metabolism Literature review

In this review the authors compare the hepatic cytochrome P 450 enzyme system (CYP) of non-rodent species, including the dog, pig, minipig and wild boar with that in human. The CYP system plays a major role in phase I metabolism of xenobiotics and endogenous substrates. The first three enzyme families (CYP1, CYP2, CYP3) metabolize most of the drugs used in the human and in the veterinary medicine. However it is important to note that there are significant variations in the substrate specificities and catalytic activities of these hepatic isoenzymes. Therefore, the same drug can cause different effects in humans and in animals, thus it necessitates the appropriate animal models for pharmacokinetic examinations, especially when experimental findings obtained in animals would be extrapolated to human application. On the other hand, some CYP isoenzymes of the animals appear to be orthologues of the human CYP isoenzymes, which means that they have the same substrate specificity. In addition, there could be interindividual differences in the activities of some CYP isoenzymes, which might point out the need for application of individually tailored drug therapy, especially in the presence of single nucleotide polymorphism (SNP). In these cases, the plasma concentrations of the administered medicine can be suboptimal or toxic, thus leading to the occurrence of drug side effects. Some studies show that the complete deficiency of certain CYP isoenzymes occurs in humans and in some dog breeds. CYP2B11 deficiency is the major cause of the prolonged awakening phase in greyhounds after administration of intravenous anaesthetics, such as propofol. It is also important to emphasize the differences among breeds and genders, e.g. testosterone can influence the level of CYP1A2, CYP2A and CYP2E1 isoenzymes in swine.