clozapine and Pneumonia--Bacterial

Stress-induced changes in pharmacokinetics can significantly alter the plasma levels of some drugs such as clozapine. This report describes the case of a middle-aged man with schizoaffective disorder, bipolar type who showed sustained elevation in clozapine levels 3 days after discontinuation. Before the clozapine levels were drawn, he had developed acute bacterial pneumonia and signs of acute bacterial meningitis followed by neuroleptic malignant syndrome after he received multiple doses of intravenous haloperidol for worsening psychosis and aggressive behavior. Existing literature on this topic is also reviewed to investigate potential reasons for sustained clozapine levels during acute inflammatory stress and neuroleptic malignant syndrome.

Topics: Acute Disease; Antipsychotic Agents; Clozapine; Humans; Male; Meningitis, Bacterial; Middle Aged; Neuroleptic Malignant Syndrome; Pneumonia, Bacterial; Psychotic Disorders

Three case vignettes are presented documenting the rise in serum clozapine that occurred at a time of acute infection in these patients. The literature on this phenomenon is scant. The physiological processes that occur in the acute phase of the inflammatory response are summarized and provide an explanation of how clozapine levels may rise in response to infection. The risk of clozapine toxicity occurring in association with infections is highlighted.

Topics: Adult; Antipsychotic Agents; C-Reactive Protein; Clozapine; Drug Therapy, Combination; Escherichia coli Infections; Female; Humans; Leukocyte Count; Male; Middle Aged; Pneumonia, Bacterial; Psychoses, Substance-Induced; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Urinary Tract Infections

Clozapine has a narrow therapeutic range. The threshold value for plasma concentrations is 350 μg/l. If plasma concentrations exceed that value, serious side-effects can occur. An increase in plasma concentrations can occur as a result of inflammatory processes which may or may not be caused by an infection. Two cases are discussed in which the plasma concentration of clozapine increased as a result of an inflammatory reaction and signs of intoxication were observed. These developments seemed to be due to cholecystitis and bacterial pneumonia respectively. The clinical presentation and pathophysiology are discussed in relation to inflammatory processes.

Topics: Adult; Antipsychotic Agents; Cholecystitis; Clozapine; Drug Monitoring; Humans; Male; Middle Aged; Pneumonia, Bacterial; Schizophrenia

Concentrations of serum clozapine, C-reactive protein (CRP) and alpha1 acid glycoprotein were greatly increased during a bacterial pneumonia in a 53-year-old woman. As the pneumonia subsided, and CRP and alpha1 acid glycoprotein normalised, serum clozapine concentration also decreased to the previous level. An increased serum clozapine and a lowered N-desmethylclozapine to clozapine ratio during the infection suggest a decreased cytochrome P(450) (CYP)1A2 activity. Cytokine-mediated CYP1A2 suppression is discussed.

Topics: Antipsychotic Agents; C-Reactive Protein; Clozapine; Female; Humans; Middle Aged; Orosomucoid; Pneumonia, Bacterial; Schizophrenia