Acyl Glucuronidation and Glucosidation of Pranoprofen, a 2-Arylpropionic Acid Derivative, in Mouse Liver and Kidney Homogenates
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The formation of acyl glucuronide and glucoside of 2-(5H-[1] benzopyrano [2,3-b] pyridin-7-yl) propionic acid (pranoprofen), an anti-inflammatory drug, was studied in homogenates and microsomes of mouse tissues by using S (+)-, R (-)-and RS (±)-pranoprofen. Acyl glucuronidation occurred mainly in the liver, whereas acyl glucosidation was predominant in the kidney. Furthermore, both conjugations occurred by enzymatic transfer of glucuronic acid of uridine diphosphate glucuronic acid (UDPGA) and glucose of uridine diphosphate glucose (UDPG) to pranoprofen, respectively. No conjugation reactions were observed in the lung, plasma or gut. The amount of conjugates in the liver and kidney increased by the prolongation of the incubation times and reached the maximum at 15-30 min for glucuronidation and 45 min for glucosidation. After that, both conjugates decreased with the lapse of time. Both acyl conjugates were the least stable in the liver, then in the kidney and the most stable in the plasma. In the liver, acyl glucoside was converted to acyl glucuronide and pranoprofen in the presence of UDPGA, but only a small amount of acyl glucuronide was changed to acyl glucoside in the kidney in spite of the presence of UDPG. In the kindney, acyl glucoside decreased relative to acyl glucuronide at increasing doses for both S (+)-and R (-)-pranoprofen, but the concentration of acyl glucoside was much higher for S (+)-pranoprofen than R (-)-enantiomer 1 h after the oral administration of S (+)-and R (-)-pranoprofen. No acyl glucoside was detected in the liver and plasma. Although only a small difference in acyl glucuronidation in the liver was observed between S (+)-and R (-)-enantiomers, acyl glucosidation in the kidney occurred more predominantly for S (+)-pranoprofen than for the R (-)-enantiomer.
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関連論文
- Dose-Dependent Shift in Acyl Glucuronidation and Glucosidation of Pranoprofen, a 2-Arylpropionic Acid Derivative, in Mice in Vivo
- Acyl Glucuronidation and Glucosidation of Pranoprofen, a 2-Arylpropionic Acid Derivative, in Mouse Liver and Kidney Homogenates
- Species Differences in Absorption, Metabolism and Excretion of Pranoprofen, a 2-Arylpropionic Acid Derivative, in Experimental Animals