title: Clinical pharmacokinetics of clozapine in chronic schizophrenic patients.
abstract: The clinical pharmacokinetics of clozapine, an atypical neuroleptic, was evaluated in 10 chronic schizophrenic male patients after intravenous and oral administration. The mean equilibrium-state concentration ratio between blood and plasma was experimentally determined to be 0.87. The average values for blood clearance, hepatic extraction ratio and oral bioavailability were 250 ml/min, 0.2 and 0.27, respectively. Plasma concentration peaked on average at 3 h. The mean volume of distribution at steady-state and the terminal half-life was 1.6 l/kg and 10.3 h, respectively. A large fraction of the dose is most probably metabolized by some extrahepatic presystemic routes. The large inter-individual variability in the bioavailability and clearance is probably the main reason for large variation in the steady-state plasma level in patients receiving the same oral dosage regimen.
authors.affiliation: Department of Biopharmaceutics and Pharmacokinetics, University of Uppsala, Sweden.
authors.forename: Y F
authors.initials: YF
authors.lastname: Cheng
authors.forename: T
authors.initials: T
authors.lastname: Lundberg
authors.forename: U
authors.initials: U
authors.lastname: Bondesson
authors.forename: L
authors.initials: L
authors.lastname: Lindström
authors.forename: J
authors.initials: J
authors.lastname: Gabrielsson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D002908:Chronic Disease; D003024:Clozapine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003984:Dibenzazepines / Q000493:pharmacokinetics*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D003984:Dibenzazepines; D003024:Clozapine