Blood levels of reduced haloperidol versus clinical efficacy and extrapyramidal side effects of haloperidol

• Published in: Progress in neuro-psychopharmacology & biological psychiatry Vol. 21; no. 2; pp. 299 - 311
• Main Authors: LANE, H.-Y, LIN, H.-N, HU, O. Y.-P, CHEN, C.-C, JANN, M. W, CHANG, W.-H
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.02.1997
• Subjects: Adolescent; Adult; Biological and medical sciences; Drug toxicity and drugs side effects treatment; Extrapyramidal Tracts - drug effects; Female; Haloperidol - adverse effects; Haloperidol - blood; Haloperidol - pharmacology; Humans; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Toxicity: nervous system and muscle; Human; Nervous system diseases; Metabolite; Neuroleptic; Psychotropic; Treatment efficiency; Metabolism toxicity relation; Oral administration; Schizophrenia; Butyrophenone derivatives; Haloperidol; Metabolism; Cerebral disorder; Psychosis; Chemotherapy; Activity concentration relation; Central nervous system disease; Pharmacokinetics; Extrapyramidal syndrome
• ISSN: 0278-5846
• DOI: 10.1016/S0278-5846(97)00007-9

1. The studies of relationships between blood levels of reduced haloperidol HL (RH) and clinical efficacy in haloperidol (HL)-treated patients have yielded variable results. On the other hand, the contribution of RH upon HL's extrapyramidal side effects (EPS) had been suggested in animal models as well as in preliminary clinical studies with limited subjects. 2. This study explored the relationships between blood drug levels and clinical effects and EPS of HL in 48 Chinese acutely exacerbated schizophrenic inpatients. After a single-blind placebo period of one week, the patients were treated with a fixed dose 10 mg of HL for two weeks. Steady-state levels of HL and RH in plasma (n = 48) and in red blood cells (RBC) (n = 37) were measured by high performance liquid chromatography. 3. The mean RH/HL ratio in RBC in the Chinese (0.55) is lower than that in non-Chinese patients as reported in the literature (> 2), so is the RH/HL ratios in plasma. 4. No significant relationship emerged between percent improvement in BPRS total score and any of drug indices (HL, RH, sum of two compounds (HL+RH), and RH/HL ratio) in plasma and in RBC. Furthermore, the responders did not differ significantly from the nonresponders in each drug index. 5. Plasma RH levels were significantly higher in 30 patients experiencing EPS compared with the other 18 patients (mean 2.14 +/- 1.71 (S.D.) ng/ml vs. 1.38 +/- 0.37 ng/ml, p < 0.05). No significant differences in other drug indices were noted between subjects with or without EPS.