Bioavailability and In-vivo Transdermal Delivery of Haloperidol

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.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

Antimutagenic constituents from Monanthotaxis caffra (Sond.) Verdc.

OBJECTIVES : Monanthotaxis caffra (Sond.) Verdc. (Annonaceae) has been reported to possess antitumoural properties. Preliminary screening showed that the crude methanolic leaf extract had strong antimutagenic effects against aflatoxin B1‐induced mutagenicity. The aim of this study was to isolate and evaluate the antimutagenic properties of the active constituents from M. caffra. METHODS : Different chromatographic, spectroscopic and spectrometric techniques were used for the isolation and identification of the antimutagenic constituents. The antimutagenic effect of the extract and compounds was evaluated using Ames, Vitotox and Comet assays. KEY FINDINGS : Bioassay‐guided fractionation of the methanolic leaf extract yielded two antimutagenic compounds identified as (+)‐crotepoxide and 5,6‐diacetoxy1‐benzoyloxymethyl‐1,3‐cyclohexadiene. Crotepoxide had strong antimutagenicity in the Vitotox assay with an IC50 value of 131 μg/ml. 5,6‐Diacetoxy‐1‐benzoyloxymethyl‐1,3‐cyclohexadiene showed strong antimutagenic activity in the Ames assay with an IC50 value of 348.9 μg/plate and no antimutagenic activity in the Vitotox test. Furthermore, the compound was able to inhibit, block or prevent biotransformation of aflatoxin B1 by repressing the proteins involved in transcription. CONCLUSIONS : Crotepoxide and 5,6‐diacetoxy‐1‐benzoyloxymethyl‐1,3‐cyclohexadiene have the potential to mitigate the risks arising from consumption of aflatoxin B1‐contaminated food and feed.The National Research Foundation under grants (CPRR 87746 and NRF/FWO 87964), Fonds Weten-schappelijk Onderzoek (FWO) under grant (G001014N), Flemish Interuniversity Council (VLIR) under grant (ZEIN2014Z184) and Agricultural Research Council (ARCOVI).http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)2042-71582019-07-01hj2018Paraclinical Science