Summary
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.
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Cheng, Y.F., Lundberg, T., Bondesson, U. et al. Clinical pharmacokinetics of clozapine in chronic schizophrenic patients. Eur J Clin Pharmacol 34, 445–449 (1988). https://doi.org/10.1007/BF01046700
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DOI: https://doi.org/10.1007/BF01046700