Pharmacoclinical correlations in schizophrenic patients treated with haloperidol 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 the theoretically recommended factor of 20. 2. The best dose (mg/kg)-concentration correlations were found for haloperidol (HAL) and reduced HAL (RHAL) in the red blood cells (RBC) (representative of the free drug fraction) rather than in the plasma of patients that had attained the steady state (at the third cycle and afterwards) 3. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the BPRS and determinations of plasma levels of total, free and conjugated homovanillic acid (HVA), a marker of central dopaminergic activity. 4. A between groups comparison at the steady state (patients (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 comparison with oral administration, at least by half. 5. Plasma HVA values complete the information provided by plasma and more especially RBC HAL and RHAL levels. All these results taken together, as substantiated by the clinical assessment scales (BPRS), assure a better pharmacoclinical surveillance and can be predictive of a patient's response.
Aymard
N
N
Unité de Pharmacologie, Centre Hospitalier Sainte-Anne, Paris, France.
Viala
A
A
Stein
I
I
Caroli
F
F
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use*; D010054:Brief Psychiatric Rating Scale; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D006719:Homovanillic Acid / Q000097:blood*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D013997:Time Factors
D014150:Antipsychotic Agents; C033563:haloperidol decanoate; D006220:Haloperidol; D006719:Homovanillic Acid