HPL Inhibition by Orlistat

This dependence of HPL inhibition by orlistat in the presence of bile salts in the incubation medium might be attributable to a better interfacial qualil/ of orhstat by the formation of mixed micelles with bile salts, which may improve the h-pase adsorption onto these mixed micelles and/or interaction with orhstat. 

With the liquid meal, the duodenal lipolysis (Tab. 10.6) decreased only slightly when micronized orlistat powder was pre-mixed with the meal (74.5% of controls), and did not decrease at all when Xenical pellets were added in the course of the administration of the meal (115.7% of controls). The differences between treated and control groups were not significant. This lack of effect of orlistat as means of reducing fhe duodenal lipolysis was not correlated with the high level of HPL inhibition observed in fhe duodenal contents (Tab. 10.5). These paradoxical results were however supported and explained by fhe results of further in vitro experiments. The rates of HPL inhibition by orlistat were found to be similar wifh bofh types of meals (half-inhibihon time=5-6 min), but the finely pre-emulsified TG of fhe liquid meal were rapidly hydrolyzed by HPL before the enzyme was sig-nificanfly inhibited by orlistat (Carriere et al., 2001). 

Wifh the solid meal, fhe in vivo duodenal hpolysis was highly and significantly reduced by orlistat wifh both forms of the drug (32.6 to 37.6% of controls Tab. 10.6), and in fhis case, a good correlation was observed with the high level of HPL inhibition (51.2 to 82.6% Tab. 10.5). In vitro experiments revealed that with the mixed solid/liquid meal, the rate of hydrolysis of the meal TG by HPL was slower fhan fhe rate of HPL inhibition by orlistat (Carriere et al., 2001). 

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