EFFECT OF RIFAMPIN ON THE PLASMA-CONCENTRATION AND THE CLINICAL EFFECT OF HALOPERIDOL CONCOMITANTLY ADMINISTERED TO SCHIZOPHRENIC-PATIENTS

We assessed the changes of plasma haloperidol concentrations and clini cal responses repeatedly np to 4 weeks after coadministration or disco ntinuation of rifampin in 12 schizophrenic patients taking haloperidol alone (group I) and 5 patients taking haloperidol and antituberculoti c drugs (group II). After coadministration of rifampin in group I, dai ly trough haloperidol concentrations rapidly decreased and reached 63% of baseline level by day 3, 41.3% by day 7, and 30% by day 28. On the other hand, after discontinuation of rifampin in group II, plasma hal operidol concentration increased to 140.7% of baseline level by day 3, 228.7% by day 7, and 329% by day 28. In this study, a 30% or greater change in the clinical rating scale was considered a positive clinical response of the drug interaction. Using this criterion, 50% of the gr oup I subjects responded according to the Brief Psychiatric Rating Sca le (BPRS) total score, and 25% responded according to the BPRS subscal e for psychiatric symptoms. No positive responses were observed in gro up II patients. These results strongly suggest that rifampin interacts with the clinical effects as well as the plasma concentrations of coa dministered haloperidol, and careful monitoring should be considered w hen coadministration or discontinuation of rifampin is needed in a sch izophrenic patient taking haloperidol.