PHARMACOCLINICAL, CORRELATIONS IN SCHIZOPHRENIC-PATIENTS TREATED WITHHALOPERIDOL DECANOATE - CLINICAL-EVALUATIONS, CONCENTRATIONS OF PLASMA AND RED-BLOOD-CELL HALOPERIDOL AND ITS REDUCED METABOLITE, AND PLASMA HOMOVANILLIC-ACID

1. The aim of this open study was to determine whether a more rational therapeutic approach could be devised for psychotic patients (n = 11) treated for long periods with long-acting (LA) haloperidol. The mean multiplication factor for the transition from the oral formulation to the long-acting one was 12.8 (10.4, standard deviation), lower than th e theoretically recommended factor of 20. 2. The best dose (mg/kg)-con centration correlations were found for haloperidol (HAL) and reduced H AL (RHAL) in the red blood cells (RBC) (representative of the free dru g fraction) rather than in the plasma of patients that had attained th e steady state (at the third cycle and afterwards) 3. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grad ing using the BPRS and determinations of plasma levels of total, free and conjugated homovanillic acid (HVA), a marker of central dopaminerg ic activity. 4. A between groups comparison at the steady state (patie nts (n = 20) with oral administration and the above patients (n = 11) with long-acting form of HAL), showed that the plasma and RBC RHAL/HAL ratios of long-acting HAL decreased significantly (p < 0,005) in comp arison with oral administration, at least by half. 5. Plasma HVA value s complete the information provided by plasma and more especially RBC HAL and RHAL levels. All these results taken together, as substantiate d by the clinical assessment scales (BPRS), assure a better pharmacocl inical surveillance and can be predictive of a patient's response.