Toxic interactions between clozapine and ampicillin

Severe adverse side effects have recently been reported after co-administration of the drugs, ampicillin and clozapine, to a schizophrenic patient. In the present work, conductimetric results indicate that ampicillin and clozapine form a 1:2 charge transfer complex which tends to associate together in water. In contrast, a charge transfer complex with a stoichiometric ratio of 2 moles ampicillin to 1 mole clozapine is obtained when the conductimetric experiment is carried out using acetonitrile as a solvent. Also, the complex appears to dissociate easily in the non-aqueous solution. Nevertheless, in both systems, unexpectedly high capacitance readings were obtained, indicating an adsorption phenomenon of the drugs on electrode surfaces. Further, conductimetric results obtained in water and with Sonification yields a 1:1 ampicillin to clozapine mole ratio. Such results were used to infer the formation of micelles in aqueous solutions. The observed change in stoichiometric ratio of the ampicillin-clozapine complex in aqueous and non-aqueous systems was then used to suggest the action of the drugs on the surface of biomembranes.