Synthesis of haloperidol prodrugs and their hydrolysis by porcine liver esterase.
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. (1)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(-1) h(-1) (p < 0.001).
Welsh School of Pharmacy, Cardiff University, Cardiff, CF10 3NB, UK.
Andrew P
AP
Morris
Keith R
KR
Brain
Charles M
CM
Heard
D000279:Administration, Cutaneous; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004950:Esterases / Q000378:metabolism*; D006220:Haloperidol / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013552:Swine
D014150:Antipsychotic Agents; D011355:Prodrugs; D004950:Esterases; D006220:Haloperidol