Synthesis of Haloperidol Prodrugs and Their Hydrolysis by Porcine Liver Esterase

Title: Synthesis of Haloperidol Prodrugs and Their Hydrolysis by Porcine Liver Esterase

Volume: 2 Issue: 4

Author(s): Andrew P. Morris, Keith R. Brain and Charles M. Heard

Affiliation:

Keywords: Haloperidol, prodrug, ester, porcine liver esterase, transdermal, hydrolysis

Abstract: In probing enhancement of the transdermal delivery of the anti-psychotic drug haloperidol, five prodrugs (ethanoate, propanoate, butanoate, octanoate and decanoate) were synthesised and their relative rates of hydrolysis determined in the presence of porcine liver esterase (PLE), a model for cutaneous esterases. H NMR, MS and elemental analysis confirmed the successful synthesis of each prodrug in high purity, and each was found to hydrolyse in the presence of PLE with the hydrolytic rate reaching a maximum with haloperidol octanoate (C8) at 2.31 ± 0.06 nmol ml- h- (p < 0.001).

Cite this article as:

Morris P. Andrew, Brain R. Keith and Heard M. Charles, Synthesis of Haloperidol Prodrugs and Their Hydrolysis by Porcine Liver Esterase, Drug Metabolism Letters 2008; 2 (4) . https://dx.doi.org/10.2174/187231208786734111