Drug displacement from protein binding: source of the sulphadoxine liberated by phenylbutazone.

1. A quantitative study has been made of the redistribution of sulphadoxine produced by phenylbutazone in live sheep.2. From calculations based on plasma measurements, 73% of the sulphadoxine in the body can be accounted for as the sum of the plasma-bound, extracellular-free and intracellular-free drug in the whole animal. This sum is termed the accountable sulphadoxine.3. After the injection of phenylbutazone there was a large shift of sulphadoxine from the plasma-bound form into the free form. The gain in free drug significantly exceeded the loss of bound sulphadoxine from the intravascular compartment, but the discrepancy could easily be explained by displacement of some bound sulphadoxine from extravascular plasma protein.4. Phenylbutazone did not displace sulphadoxine from sheep erythrocytes in vitro, nor from homogenates of liver, kidney or skeletal muscle.5. Although the existence of other susceptible binding sites cannot be entirely excluded, this evidence strongly suggests that all the sulphadoxine liberated by phenylbutazone comes from binding sites on plasma protein.