Hydrolysis of haloperidol decanoatein vitro by cultured cells

Abstract

[14C]Haloperidol decanoate was hydrolysed by partially purified carboxylesterase but not in plasma, blood, lymph and lymphatic liquid. These fluids inhibited the enzyme-mediated hydrolysis of the ester. Within the same incubation period as above, the ester was found hydrolysed to various extents in cell cultures of isolated rat liver cells, of human and rat lymphocytes and of established cell lines (BGM cells, WI-38 cells and L6 cells). Thus, the hydrolysis of the ester was demonstrated in vitro with use of viable cell cultures instead of enzyme preparation. From the time course study on the metabolism of haloperidol decanoate in cell cultures, it was concluded that haloperidol decanoate was first concentrated in the cells and hydrolysed to haloperidol. Based on these results, the metabolic sequences in vivo leading to the formation of active principle haloperidol after intramuscular administration of its decanoate were discussed.

Absorption of intramuscularly administered [14C]haloperidol decanoate in rats

“…As shown in our separate works, haloperidol decanoate was essentially hydrolysed in intact cells (10) but not in plasma or tissue homogenate because the ester was protected by its binding to protein from esterase attack (II). Neither unchanged haloperidol decanoate nor its conjugated form was detected in rat bile and urine, but metabolites directly derived from the haloperidol were present after intramuscular administration of the ester.…”

Where does hydrolysis of nandrolone decanoate occur in the human body after release from an oil depot?

“…Hydrolysis can occur via chemical processes or by carboxylesterases (Imai and Ohura, 2010;Jewell et al, 2007;Prusakiewicz et al, 2006). These enzymes hydrolyse a different ester prodrug, haloperidol decanoate (Nambu et al, 1987;Oh-E et al, 1987). Because the ester bond in this prodrug is similar to the ester bond in ND, it is likely that ND hydrolysis also occurs by carboxylesterases.…”