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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Reversible metabolism of haloperidol and reduced haloperidol in Chinese schizophrenic patients.

Haloperidol disposition has been associated with reversible metabolism: it is reversibly reduced to its metabolite, reduced haloperidol, which has less pharmacologic activity than the parent compound. To characterize the interconversion process, six healthy male schizophrenics were administered a single dose of 10 mg haloperidol or reduced haloperidol in a randomized crossover manner. Using a general pharmacokinetic model for the interconversion process, the clearances of haloperidol and reduced haloperidol are 1.15 +/- 0.32 l/h/kg and 0.76 +/- 54 l/h/kg, respectively. These clearances are similar to that obtained by the usual mammillary model analysis. With a single 10 mg dose administration of either drug, about 23% of the biotransformation of haloperidol involves the reduction pathway. Back conversion from the reduced metabolite to the parent drug through oxidation contributes even less to the total biotransformation of reduced haloperidol. This action of interconversion or saturation under chronic drug administration is unknown. Reversible metabolism of haloperidol could partially account for the wide therapeutic range for haloperidol as reported in the literature.[1]


  1. Reversible metabolism of haloperidol and reduced haloperidol in Chinese schizophrenic patients. Jann, M.W., Lam, Y.W., Chang, W.H. Psychopharmacology (Berl.) (1990) [Pubmed]
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