Of these the most important for drug clearance belong to the CYP1, CYP2, and CYP3
There are three major CYP families that encode enzymes that play an important role in phase I metabolism: CYP1, CYP2, and CYP3
. (3) The CYP3A subfamily is the most abundant CYP enzyme and represents about 30% of the total CYP in the human liver.
Lewis, "Human cytochromes P450 associated with the phase 1 metabolism of drugs and other xenobiotics: a compilation of substrates and inhibitors of the CYP1, CYP2 and CYP3
families," Current Medicinal Chemistry, vol.
Asselah et al., "Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3
families in 22 different human tissues," Pharmacogenetics and Genomics, vol.
In animal studies, it has been found that IH-induced liver damage affects the rate of drug metabolism, such as that of theophylline, which is widely used for treating respiratory system diseases. In humans, the CYP1, CYP2, and CYP3
families are involved in hepatic drug metabolism.
On the other hand, apixaban and phenytoin share the hepatic enzyme CYP3
A4, and their concurrent use will lower its effectiveness (Lehne, 2013).
In addition to P-gp, Caco-2 cells express the metabolizing enzyme CYP3A and nuclear receptors such as pregnane X receptor (PXR), which regulate the expression of ABCB1 and CYP3
. P-gp and CYP3A interact co-ordinately at the intestinal barrier and limit drug absorption.
Over 70 CYP gene families have been described so far and are further divided into families and subfamilies of which CYP1, CPY2 and CYP3
, are involved in hepatic drug metabolism.
Those most important in drug metabolism are CYP1, CYP2 and CYP3
; out of these, six enzymes are responsible for the biotransformation of more than 90 percent of drugs undergoing phase I metabolism (see table 1, p22).
Coadministering a cytochrome P450 isoenzyme 3A4 (CYP3A4)inhibiting macrolide antibiotic, such as clarithromycin or erythromycin) (but not azithromycin) with atorvastatin (Lipitor[R]), simvastatin (Zocor[R]), or lovastatin (Mevacor[R]), which are metabolized by CYP3
A4, is associated with a fourfold to 10-fold increase in statin concentrations.