IMPORTANT METABOLITES TO MEASURE IN PHARMACODYNAMIC STUDIES OF CHLORPROMAZINE

Plasma concentrations of chlorpromazine (CPZ) and six metabolites were measured in 12 chronic schizophrenic patients on a fixed dose of CPZ. All six metabolites were measured in significant concentrations, rang ing from 12 to 57% of the parent drug concentration. They are listed i n order of decreasing mean concentration as follows: chlorpromazine-N- oxide > chlorpromazine sulfoxide > 7-OH chlorpromazine > Nor(2) chlorp romazine sulfoxide > Nor(2) chlorpromazine > Nor(1) chlorpromazine. CP Z concentrations showed significant correlation with the 7-OH chlorpro mazine metabolite concentration. Since these metabolites have been ass ociated with in vitro activity and occur in significant concentrations , it is recommended that all six metabolites be measured in studies co rrelating drug levels with pharmacodynamic effects.