DEVELOPMENTAL EXPRESSION OF CYTOCHROME-P450 ENZYMES IN HUMAN LIVER

Drug-metabolizing cytochrome P450 enzymes, the major phase I enzymes, are active in human liver already at very early stages of intrauterine development, although presumably at fairly low concentrations and in low numbers. During maturation, these enzymes go through various devel opmental programmes towards adulthood. The major increase both in abun dance as well as in number of different enzymes takes place after birt h, probably during the first year of life. Detailed information concer ning these developmental changes is still limited. The major drug-meta bolizing P450 enzymes appear to be primarily members of the CYP3A subf amily in all stages of development. The balance between different memb ers of this subfamily however, undergoes significant switches from the foetal predominant CYP3A7 to the major adult form CYP3A4. The ontogen y of the other cytochrome P450 enzymes is less well characterized, but the major switch-on appears to occur mainly after birth. Developmenta l expression of P450 enzymes is one of the key factors determining the pharmacokinetic status of developing individuals both pre-and postnat ally.