Pharmacokinetic analysis of chlorpromazine in rat serum, cerebrospinal fluid and striatum.
The time courses of the total concentration of chlorpromazine (CPZ) and its S-oxide (CPZSO) in serum after i.v. administration of CPZ are described by a two compartment model and a simple metabolism model, respectively. The time course of the free CPZ concentration in serum is predicted by the correlation between the ratio of CPZSO/CPZ and the free fraction of CPZ in serum which was established in the previous study. The time course of CPZ concentration in cerebrospinal fluid (CSF) is described by a basic physiological model in which the CSF compartment is connected with the serum compartment (free drug) by the apparent diffusion clearance. Equilibrium dialysis of the striatum homogenate was carried out to clarify the CPZ disposition in the striatum. Since the binding curves of CPZ in the striatum on the Langmuir plot and the Scatchard plot were a sigmoidal and an upward curve, the time course of the drug's concentration was analyzed on a simple kinetic model designed in conformity with a blood-flow limited model. The time course was described by a simple kinetic model for up to 8 h after CPZ administration. These pharmacokinetic models for CSF and the striatum will be used to analyze the relationship between the pharmacokinetics and pharmacodynamics of CPZ.
Sato
S
S
Department of Pharmaceutics, Niigata College of Pharmacy, Japan.
Koshiro
A
A
D000818:Animals; D001711:Biotransformation; D002746:Chlorpromazine / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D003956:Dialysis; D008297:Male; D008954:Models, Biological; D017072:Neostriatum / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002746:Chlorpromazine