Drug Metabolism Letters

Zhiyang Zhao
Amgen
Cambridge, MA
USA

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Synthesis of Haloperidol Prodrugs and Their Hydrolysis by Porcine Liver Esterase

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

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).

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

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Article Details

VOLUME: 2
ISSUE: 4
Year: 2008
Page: [275 - 279]
Pages: 5
DOI: 10.2174/187231208786734111
Price: $58