Lower Plasma Levels of Haloperidol in Smoking Than in Nonsmoking Schizophrenic Patients

Abstract

The impact of smoking on plasma haloperidol (HAL) concentrations was investigated in 66 Japanese male schizophrenic inpatients treated orally with HAL. The subjects consisted of 22 nonsmokers and 44 smokers each smoking ten cigarettes per day. Plasma concentrations of HAL were determined by an enzyme immunoassay method. There were significant positive correlations between the plasma HAL concentration and the daily dose of HAL per kg body weight (Y = 58.1X-0.01 (r = 0.86)). Smokers had significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 54.3+/-16.6 vs. 70.6+/-23.2 ng/mL/mg/kg). In doses less than 0.2 mg/kg of HAL, smokers showed significantly lower HAL concentrations per daily dose of HAL/kg body weight than nonsmokers (smokers vs. nonsmokers = 55.1+/-14.4 vs. 79.5+/-27.1 ng/mL/mg/kg), whereas no significant difference in HAL concentrations per daily dose of HAL/kg body weight was observed between smokers and nonsmokers when treated with more than 0.2 mg/kg (smokers vs. nonsmokers = 52.9+/-20.7 vs. 60.0+/-11.1 ng/mL/mg/kg). Our results indicate that smoking may induce the enzyme(s) metabolizing HAL, which results in lower plasma HAL concentrations in smokers than in nonsmokers, particularly at low doses of HAL.

Cognitive Deficits in Schizophrenia: Focus on Neuronal Nicotinic Acetylcholine Receptors and Smoking

“…A significant reduction (20-40% lower) in plasma levels is documented for clozapine (Seppala et al 1999), haloperidol (Shimoda et al 1999) and olanzapine (Zyprexa, package insert).…”

A functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene: association with tardive dyskinesia in schizophrenia

“…The plasma concentration of most typical antipsychotics is significantly reduced by smoking, [36][37][38][39][40][41] an established inducer of CYP1A2. 42 Conversely, the cessation of smoking was reported to increase chlorpromazine plasma concentration and adverse effects.…”

Lack of association between a functional polymorphism of the cytochrome P450 1A2 (CYP1A2) gene and tardive dyskinesia in schizophrenia

“…The authors pointed out that the CYP1A2 enzyme constitutes 12% of the total hepatic CYP content, which is an approximately sixfold greater amount than that of CYP2D6 [Shimada et al, 1994] and thus can be considered an important metabolic clearance pathway within the disposition of antipsychotics. Moreover, Basile et al [2000] stress the fact that smoking, which has been reported to induce CYP1A2 activity [Kalow and Tang, 1991], signi®cantly reduces the plasma concentration of most typical antipsychotics [Pantuck et al, 1982;Stimmel and Falloon, 1983;Ereshefsky et al, 1985;Jann et al, 1986;Miller et al, 1990;Shimoda et al, 1999]. Taking into consideration that a vast majority of patients suffering from schizophrenia are smokers [Hughes et al, 1986;Lohr and Flynn, 1992], Basile et al [2000] hypothesize that schizophrenic patients are likely to have both increased CYP1A2 activity and elevated CYP1A2-dependent disposition of typical antipsychotics.…”