Correlation between nortriptyline and debrisoquine hydroxylation in the human liver.

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.