Bioavailability and In-vivo Transdermal Delivery of Haloperidol

Abstract

Background: Sustained blood level with effective therapeutic blood level inpsychotic patients in the range of usual therapeutic dose is favorable.Objectives: To investigate where this sustained and effective therapeutic blood level and improve in bioavailability could be achieved by usinghaloperidol/transdermal gel formulation.Materials and Methods: In-vivo transdermal delivery of haloperidol wasstudied in rabbits comparing transdermal gel formulation containing 1, 8-cineole as penetration enhancer and oral tablet. Concentrations of haloperidol in plasma were measured by reverse phase HPLC. The pharmacokinetic parameters generated from this study were evaluatedstatistically using one-way analysis of variance (ANOVA).Result: The results showed that transdermal gel formulation increased rate and extent of absorption and improve bioavailability of haloperidol. The plasma concentrations of haloperidol were declined in biexponential fashion where the area under the curves and absorption rate Cmax/AUC elimination rate constant Kel, Tmax, mean residence time (MRT), mean absorption time (MAT), and total clearance (CLtotal) were significantly different p < 0.05, but volume of distribution (Vd) did not differ significantly p >0.05.The absolute bioavailability from the oral tablet, and the transdermal formulation was 38% and 57% respectively and highly significant P < 0.01.Conclusion: This study suggest that it is possible to achieve significant sustained therapeutic blood levels for longer time and also suggest that further human investigations of the transdermal dosage are warranted.Key words: Haloperidol/Transdermal gel formulation, Oral tablet, Rabbits, Bioavailability,Pharmacokinetic.