Thioridazine absorption

Various factors may account for the variability in response to neuroleptics. These include differences in the diagnostic criteria, concurrent administration of drugs which may affect the absorption and metabolism of the neuroleptics (e.g. tricyclic antidepressants), different times of blood sampling, and variations due to the different type of assay method used. In some cases, the failure to obtain consistent relationships between the plasma neuroleptic concentration and the clinical response may be explained by the contribution of active metabolites to the therapeutic effects. Thus chlorpromazine, thioridazine, levomepromazine (methotrime-prazine) and loxapine have active metabolites which reach peak plasma concentrations within the same range as those of the parent compounds. As these metabolites often have pharmacodynamic and pharmacokinetic activities which differ from those of the parent compound, it is essential to determine the plasma concentrations of both the parent compound and its metabolites in order to establish whether or not a relationship exists between the plasma concentration and the therapeutic outcome. 

The electronic spectral absorption properties of several 2-substituted, 10-alkylated phenothiazine derivatives, including promazine hydrochloride (PZ), 2-chlorpromazine hydrochloride (CPZ), 2-trifluoromethylpromazine hydrochloride (TFMPZ), 2-thiomethylpromazine (TMPZ), prochlorperazine (PCP), 2-trifluoromethylperazine dihydrochloride (trifluoperazine, TFZ), thioridazine hydrochloride (TR), fluphenazine hydrochloride (FP) and perphenazine hydrochloride (PP) (Fig. IB), were investigated in different media (acetonitrile, methanol and pH 7.4 phosphate buffer solution) by Garcia et al. [4]. 

Thioridazine impairs its own absorption at higher plasma levels possibly because of its strong anticholinergic effect, which could influence gastric emptying. 

Figure 7.11 Absorption of thioridazine in goldfish in the presence of increasing concentrations of various non-ionic detergents, the rate of absorption being proportional to the reciprocal of the death time of the fish, reciprocal death time is plotted on the ordinate concentrations of surfactants (% w/v) are marked. Lack of enhancement of absorption by some surfactants is probably due to poor ability to penetrate lipid membranes because of shape factors. Decrease in absorption is due to non-ionic micelle formation. From Florence and Gillan [41] with permission. The surfactants are all Atlas products (Honeywill-Atlas, UK).

Figure 7.13 The influence of pH and polysorbate 80 concentrations on the absorption of solutions or suspensions containing 0.08 % thioridazine as shown by reciprocal death times of goldfish. From Florence and Gillan [41] with permission.

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