Effect of simultaneous administration of drugs on absorption and excretion. XVI. Effect of probenecid on plasma protein binding of sulfadimethoxine in fast and slow acetylator rabbits.

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Two groups of rabbits categorized on the basis of their acetylation capacity were used in this study as fast and slow acetylator rabbits. The ratio of the unbound fraction of sulfadimethoxine (SDM) in plasma at 2 h after intravenous bolus injection of SDM in combination with probenecid to the unbound fraction of SDM in plasma at 2 h after intravenous bolus injection of SDM alone was determined in fast and slow acetylator rabbits. A significant difference in the ratio of unbound fraction of SDM was observed between fast and slow acetylator rabbits. This indicates that the effect of probenecid on the in vivo binding of SDM to plasma proteins is dependent on the acetylation capacity for SDM in rabbits. In addition, probenecid was found to cause a significant decrease in the plasma concentration of SDM in fast acetylator rabbits, but caused no significant change in the plasma concentration of SDM in slow acetylator rabbits.

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