INDUCTION OF CYP2D6 IN PREGNANCY

Expression of the drug-metabolizing enzyme cytochrome P4502D6 (CYP2D6) is predominantly under genetic control, and enzyme-inducing drugs hav e little influence on its activity, We studied the activity of CYP2D6 during pregnancy, One hundred forty pregnant women were genotyped for CYP2D6, Seventeen of them (four poor metabolizers, seven heterozygous extensive metabolizers, and sis extensive metabolizers) were phenotype d with dextromethorphan in late pregnancy and 7 to 11 weeks after part urition, During pregnancy the dextromethorphan/dextrorphan metabolic r atio was significantly reduced (p = 0.0015) among homozygous and heter ozygous extensive metabolizers, indicating increased CYP2D6 activity, In contrast, poor metabolizers showed an increased metabolic ratio dur ing pregnancy. These results are consistent with previous findings of a marked increase in metabolism of the CYP2D6 substrate metoprolol dur ing pregnancy, Both studies indicate an increase in CYP2D6 activity du ring pregnancy, which may be caused by an induction of the CYP2D6 enzy me.