Search for: [Abstract = "One of the most important process affects the fate of the drug in the body is elimination. The aim of the presented study was to determine the hepatic DL76 elimination kinetics by usage of the isolated perfused rat liver. Compound DL76 \(1\-\[3\-\(4\-tert\-butylphenoxy\)propyl\]piperidine\) is an example of new nonimidazole selective histamine H3 receptor antagonist. In order to achieve the aim of the study the binding rate of DL76 to serum proteins was assessed in vitro applying equilibrium dialysis technique, and the internal clearance of DL76 was determined by hepatic microsomal fractioning. Based on these data two mathematically modeled hepatic clearance simulations were conducted\: \"well stirred\" and \"parallel tube\". On the next step the quantitative assessment of the hepatic metabolic process was performed to obtain hepatic clearance of DL76 ex vivo using IPRL model. The received values of hepatic clearance were compared with the predicted ones and with the total body clearance of the DL76 tested in vivo. Concentrations of DL76 compound were determined using LC\/MS\/MS. The results show that biotransformation of DL76 in the liver may play an important role in its elimination process from the body due to significant contribution of the hepatic clearance in the total clearance of DL76. The obtained results indicate that DL76 is extensively bound to serum protein. The investigated compound belongs to the group of drugs with intermediate hepatic extraction ratio. Simulation of hepatic clearance, taking into account such factors as the rate of blood flow through the organ, the drug protein binding and enzymatic activity was confirmed ex vivo."]

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