Variation in the single dose pharmacokinetics of fluphenazine in psychiatric patients

The single dose pharmacokinetics of fluphenazine (2 x 5 mg tablets, Prolixin) were studied in 21 drug free male psychiatric patients (12 black, 9 white). Plasma samples were harvested over a period of 48 h while the patients were on a strictly controlled diet. The results showed wide interpatient variations in all pharmacokinetic parameters including Cmax, AUC, apparent oral clearance, and elimination half-life. It was determined for each of these parameters that the geometric mean gave a better estimate of central tendency than the corresponding arithmetic mean and the distribution was skewed and leptokurtotic. There was no significant difference between blacks and whites in any pharmacokinetic parameter examined. Considerable variations and marked undulations in the elimination portion of the plasma concentration versus time profiles were evident, possibly indicating biliary recycling of the drug. These undulations made it difficult to determine elimination rate constants for several of the patients. Hydrolysis or plasma samples from one patient demonstrated that the conjugate(s) of fluphenazine was present in three to four times the concentration of the unchanged drug.