Metabolism of Chlorpromazine and p‐Nitrobenzoic Acid in the Liver, Intestine and Kidney of the Human Foetus

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Abstract
The ability of the liver, intestine and kidney to metabolize chlor‐promazine (CPR) and p‐nitrobenzoic acid (NBA) was studied in the human foetus. Low levels of CPR metabolizing activity were present in all the tissues studied, but only the liver and intestine were capable of metabolizing NBA. We were not able to detect any cytochrome P‐450 in the liver microsomal fraction. The enzymes metabolizing CPR and NBA are located in the liver microsomes, they require NADP and the 100,000 × g supernatant fraction or NADPH2 for full activity, are inhibited by carbon monoxide, and have Michaelis constants of the same order of magnitude as found in the enzymes from experimental animals. The above mentioned characteristics of the foetal enzymes strongly suggest that they belong to the same class of NADPH2‐dependent mixed function oxidases which are detected in the livers of adult humans and animals and which are thought to be responsible for the greater part of oxidative and reductive drug metabolism.

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