Interindividual variation of plasma haloperidol concentrations and the impact of concomitant medications: the analysis of therapeutic drug monitoring data.
We analyzed therapeutic drug monitoring (TDM) data from 231 schizophrenic inpatients (137 men, 94 women) and investigated interindividual differences of plasma haloperidol (HAL) concentrations and drug/drug interactions between HAL and various concomitant drugs. Plasma HAL concentrations were determined by an enzyme immunoassay (EIA) method. Plasma HAL concentrations per daily dose of HAL per body weight (HAL C/D ratio) demonstrated an approximately 11-fold interindividual variation. The patient subjects who received carbamazepine (CBZ) concomitantly had a mean HAL C/D ratio that was 37% lower than that of the patient subjects without CBZ. The patient subjects treated with concomitant phenobarbital (PB) also showed a mean HAL C/D ratio that was 22% lower than those without PB. We concluded that careful evaluation of HAL TDM data and consideration of the impact of concomitant medication such as CBZ or PB that might influence the metabolism of HAL is necessary in daily clinical settings to avoid insufficient clinical response because of lowered concentrations of HAL or adverse effects because of high concentrations of HAL.
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
G
G
Hirokane
T
T
Someya
S
S
Takahashi
S
S
Morita
K
K
Shimoda
D000368:Aged; D018692:Antimanic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002220:Carbamazepine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D014644:Genetic Variation / Q000502:physiology; D006220:Haloperidol / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D002220:Carbamazepine; D006220:Haloperidol