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Pipequaline Transport from Blood to Brain and Liver: Role of Plasma Protein‐bound Drug

Brain uptake of pipequaline (45319 RP) has been studied in‐vivo after a single capillary transit by intracarotid injection to rats. Pipequaline is extensively bound to plasma proteins: i.e. human serum albumin (HSA), α1‐acid glycoprotein (AAG), lipoproteins and blood cells, mainly erythrocytes. The dialysable drug fraction as measured in‐vitro by equilibrium dialysis at 37°C, was inversely related to the concentration of binding component. Similarly, the brain uptake of pipequaline was inversely related to the protein concentration of the injected solution. However, the measured brain uptake of pipequaline was higher than those predicted by in‐vitro measurements of dialysable drug for all proteins and erythrocytes, except HSA. These results show that a fraction of bound pipequaline as measured in‐vitro is available for transport through the blood brain barrier. HSA‐bound pipequaline is an exception as it is restricted to the vascular space. Pipequaline was totally cleared by the liver through a single passage.