Blood to brain distribution of neuroleptics

Knowledge of the tissue distribution of drugs is important in interpreting other more commonly measured pharmacokinetic parameters, such as levels of drug in blood. For the neuroleptics, studies of blood to brain distribution are few and, due to technical differences between studies, the results are neither consistent within drugs nor comparable between drugs. We estimated the plasma to brain distribution of several common neuroleptics in rats using a single technique, the radioreceptor assay for neuroleptics. At doses that led to plasma levels similar to those achieved in clinical use, brain to plasma ratios ranged from 34 and 22 for fluphenazine and haloperidol, respectively, to 2.2 and 0.97 for thioridazine and mesoridazine, respectively. In general, clinical milligram potency and the favorability of distribution to brain ranked in the same order. These results may explain why such low levels of the high potency neuroleptics and such high levels of the low potency neuroleptics, greater than can be explained by relative differences between the same drugs in potency in vitro, are observed in blood both by radioreceptor and chemical assay techniques.