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The benzylic hydroxylation of nortriptyline (NT) and debrisoquine (D) by isolated human liver microsomes from eight subjects was studied. There was a strong correlation between the 10-hydroxylation of NT and the 4-hydroxylation of D (r = 0.96). The ability to hydroxylate D was also measured in vivo as the ratio between D and 4-OH-D in urine after oral administration of the drug to four subjects. This estimate of hydroxylation capacity agreed with the in vitro measurements. Liver microsomes from a subject defined as a poor in vivo oxidizer of D hydroxylated NT and D unusually slowly. Separation of microsomal proteins by SDS-gel electrophoresis indicated a relative lack of a cytochrome P-450 isozyme with a molecular weight of 54,500 in the liver from the poor oxidizer.
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