Haloperidol high concentrations

Figure 4.19 The stabilizing and lytic effects of various tranquilizers and antihistamines on human erythrocytes. Stabilization of the erythrocytes against hypotonic haemolysis is caused by butyrylperazine dimaleate, prochlorperazine ethane disulphonate, fluphenazine diHCl, reserpine phosphate, thioridazine HCl, trifluoperazine diHCl, chlorpromazine HCl, promethazine HCl, and haloperidol. High concentrations of all the compounds caused direct lysis. Stabilization by chlorpromazine sulphoxide occurred at concentrations higher than equiosmolar concentrations of NaCl or sucrose. All the compounds were dissolved in aqueous solution except haloperidol which was added to the final aqueous solution from concentrated stock ethanolic solutions. The final concentration of the erythrocytes was 2.4 x 10 cells ml A relative haemolysis of 1.0 indicates an absolute degree of haemolysis of around 40%. From Seeman and Weinstein [158] with permission.

High doses of imipramine, haloperidol, and chlorpromazine (at 1 jM concentrations) are known to inhibit GABA release in vitro. Baclofen, [P-(p-chlorophenyl)-GABA] (4.171), is a valuable compound which enhances GABA release and is therefore an indirect agonist. 

The serum concentrations of "classical neuroleptics and their metabolites vary considerably in patients, even when the dose of drug administered has been standardized. Such interindividual variation may account for the differences in the therapeutic and side effects. High interindividual variations in the steady-state plasma levels have been reported for pimozide, fluphenazine, flupenthixol and haloperidol, some of these differences being attributed to differences in absorption and metabolism between patients. 

Roh H-K, Chung J-Y, Oh D-Y, Park C-S, Svensson J-O, Dahl M-L, Bertilsson L. Plasma concentrations of haloperidol are related to the CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients. Br J Clin Pharmacol 2001 52 265-271. 

L. Pan, M.T. Rosseel and F.M. Belpaire, Comparison of two high-performance liquid chromatographic methods for monitoring plasma concentrations of haloperidol and reduced haloperidol, Ther. Drug Monit., 1998, 20, 224—230. 

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