Active products of fetal drug metabolism.

Abstract

Theoretical relationships between the activities of placental and fetal enzymes and their ability to perturb the steady‐state tissue levels of drugs have been calculated. Although the calculations suggest that the activities of the enzymes that metabolize desipramine and 3,4‐benzpyrene in human placentas and fetuses may be high enough to decrease the steady‐state concentrations of these substances, the rates of metabolism of most drugs are probably too slow to affect the fetal levels of most lipid‐soluble compounds. It is also probable that the rate of bromobenzene metabolism by cytochrome P‐450 enzymes in fetal liver is too slow to cause liver necrosis caused by this toxicant. Nevertheless, it is possible that enzymes that catalyze the reduction of nitro compounds, such as nitrofurazone, to hydroxylamino derivatives may mediate various drug toxicities in fetuses.