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Therapeutic drug monitoring data: No influence of amisulpride on clozapine plasma concentration
The atypical antipsychotic amisulpride, a substituted benzamide, is eliminated unchanged mainly through the kidneys. Hepatic metabolism via the cytochrome P450 system is only of minor significance. Little is known, however, about how the interaction with other drugs affects the pharmakokinetics of amisulpride. In contrast to amisulpride, the tricyclic dibenzodiazepine clozapine is metabolized almost completely via the cytochrome P450 system before it is eliminated. Clozapine plasma concentrations are influenced by a large number of drugs, and, in turn, clozapine affects the plasma concentration of other substances. Recently, however, an increase in the dose-corrected amisulpride plasma concentration was observed after administering clozapine. This was thought to be caused by an interaction during renal elimination. The exact mechanism of renal amisulpride excretion is still unclear, however, an active secretion of the drug via cation-proton-antiporters is likely. Since clozapine and its major metabolites are considered substrates of the same transporter family, competitive inhibition of active elimination of amisulpride by clozapine and its metabolites may explain the effects of clozapine co-medication on amisulpride plasma levels.
With respect to this observation, we set out to clarify whether amisulpride also affects the clozapine plasma concentration.
Clozapine plasma concentrations in 13 patients between 19 and 47 years of age (6 female, 7 male) who had insufficiently responded to clozapine were monitored when receiving amisulpride as co-medication.
No changes in the dose-corrected clozapine plasma concentrations could be demonstrated while administering amisulpride. This result is discussed with respect to the clinical relevance of co-medication with amisulpride and clozapine and the supposed renal mechanisms considered.