Effect of long‐term phenothiazine treatment on drug metabolism.

1 The half‐life of plasma antipyrine was measured in twelve chronic schizophrenic patients during long‐term phenothiazine treatment and again following 4‐5 weeks on placebo. 2 The mean antipyrine half‐life was low during phenothiazine administration (6.1 +/‐ 4.2 h), rising after withdrawal of drugs to the range reported for untreated subjects by other authors (9.5 +/‐ 4.2 h). The prolongation of antipyrine half‐ life following the drug‐free period occurred in nine of twelve subjects and the difference was significant for the group at P less than 0.05. 3 The finding suggests that prolonged administration of phenothiazines stimulates the rate of drug metabolism.