Enterocytic CYP3A4 in a paediatric population: developmental changes and the effect of coeliac disease and cystic fibrosis

Aims To investigate the effects of age and disease states on the expression and activity of intestinal CYP3A4 in a paediatric population. Methods Duodenal biopsies and surgical sections were collected from 104 pae diatric patients (age range 2 weeks to 17 years) and from 11 foetuses. An S 9 fraction was prepared in each case. CYP3A4 expression was assessed by Wes tern blotting and by immunohistochemistry; activity was measured by the rat e of formation of 6 beta -hydroxytestosterone from testosterone. Villin exp ression was used as a marker of enterocyte harvest to normalize CYP3A4 expr ession and activity data. Results In the 74 histologically normal paediatric biopsies there were stat istically significant increases in CYP3A4 expression (r(2)=0.19, P=0.001) a nd activity (r(2)=0.17, P=0.02) with age. CYP3A4 was practically absent in fetal duodenum and was expressed at relatively low levels in neonates (P<0. 05 between neonates and children >5 years). Active coeliac disease resulted in significant (P<0.001) decreases in CYP3A4 expression and activity. Conclusions Duodenal CYP3A4 is present at significantly lower levels in neo nates and in patients with active coeliac disease. This may have clinical s ignificance with respect to the oral bioavailability of CYP3A4 substrates.