This review covers some recent work on: 1. The effects of route of administration on the pharmacokinetics of
fluphenazine and some of its metabolites; 2. The clinical pharmacokinetics of
fluphenazine in acute patients medicated with oral
fluphenazine; 3. The clinical pharmacokinetics of
haloperidol in acute patients medicated with oral
haloperidol; 4. The clinical pharmacokinetics of
fluphenazine in the maintenance of individuals with chronic
schizophrenia with
fluphenazine decanoate; 5. A systematic
dose reduction study in maintenance treatment refractory patients with oral
haloperidol. A study in which plasma levels of
fluphenazine and
fluphenazine sulfoxide were measured in a group of DSM-III-R patients with
schizophrenia before and after switching from oral
fluphenazine to depot
fluphenazine, decanoate revealed much higher levels of
fluphenazine sulfoxide with oral medication compared with those found with depot
fluphenazine. These data illustrate the effect of "first pass" metabolism after oral
fluphenazine. Thus in a group of 33 patients randomly assigned to receive 5 mg, 10 mg or 25 mg oral
fluphenazine daily, steady state plasma
fluphenazine levels at each dose were significantly lower that those of
fluphenazine sulfoxide or 7-hydroxy-fluphenazine, although there were no significant differences between the levels of
fluphenazine and
fluphenazine N4-oxide. On the other hand, plasma levels of the parent
drug were significantly higher than those of any metabolite in a corresponding group of patients at steady state on depot medication. These observations underscore the importance of route dependent differences in the pharmacokinetics of
fluphenazine which can lead to problems when switching patients from oral to depot
neuroleptics. The concept of "disabling side-effects" is an important development in understanding relationships between plasma levels of
neuroleptic drugs and clinical response in patients with
schizophrenia. Risk-benefit analysis shows clearly that evaluation of relationships between plasma levels and clinical response must take into account the consequences of side-effects which the patient feels have a negating effect on
therapy. Emerging data on putative therapeutic plasma level ranges in maintenance
therapy are potentially important and may be particularly useful in the maintenance of patients on low dose
therapy. It is noteworthy that in a carefully executed
dose reduction study in treatment resistant patients under medication with
haloperidol, the mean lowest effective dose (8.7 ng/mL) lay within the optimal therapeutic range (5 ng/mL to 12 ng/mL) found in acutely psychotic patients. The study showed that gradual
dose reduction of
neuroleptic was possible in chronic treatment resistant patients with
schizophrenia who were originally thought by ward staff to require high doses of
neuroleptic.(ABSTRACT TRUNCATED AT 400 WORDS)