Factors affecting serum haloperidol level assessed by longitudinal therapeutic monitoring.
1. Since the development of a kit for the assay of haloperidol by enzyme immunoassay, therapeutic monitoring of haloperidol has been utilised in Japan for several years. By retrospectively analysing the accumulated data, this study was carried out to investigate the factors affecting haloperidol level. Especially, the effects of enzyme-inducing comedications were analysed in relation to serum gamma-glutamyltransferase (GGT) level, which has been measured simultaneously with haloperidol. Serum haloperidol level measurements were obtained from medical records of inpatients on multiple medications (n = 102). For each subject, average haloperidol level was computed during the same prescription and doses. The effects of age, sex, smoking status, and the coadministration of carbamazepine and barbiturates (including phenobarbital, amobarbital and pentobarbital) were analysed using correlation, between-group comparison and multiple regression analysis. Separately, the effect of comedications on haloperidol and GGT levels were analysed individually in a small number of patients (n = 5) who had received those comedications intermittently. Significant lowering of serum haloperidol level by the coadministration of carbamazepine and/or barbiturates was observed. The coadministration was also correlated with the elevated GGT level in between-group comparison. In the separate analysis, the change in haloperidol level was correlated with the change in GGT level in some individuals but not in others. None of the other clinical factors investigated in the study showed significant effect on haloperidol level. This study suggests that the lowering of haloperidol level and the elevation of GGT level may often occur coincidentally by the coadministration of enzyme-inducing drugs. However, whether there is a causal relationship between these phenomena and whether elevated serum GGT level could serve as a clinically useful marker need to be clarified by further basic pharmacological research.
Fukuda
R
R
Department of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan. r.fukuda@iop.kcl.ac.uk
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000097:blood* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006220:Haloperidol / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000188:drug therapy*; D012044:Regression Analysis; D012907:Smoking / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D014150:Antipsychotic Agents; D005723:gamma-Glutamyltransferase; D006220:Haloperidol