The plasma protein binding of metoclopramide was measured after addition of the drug (60 ng ml‐1) to plasma from 18 patients with renal disease and 18 age and sex matched healthy individuals. The mean free fraction in renal disease (0.59 range 0.41‐0.71) was not significantly different from controls (mean 0.6 range 0.56‐0.69). In both groups the binding ratio of metoclopramide was significantly related to plasma alpha 1‐acid glycoprotein (AAG) concentration but not to albumin or plasma non‐esterified fatty acids concentration. Metoclopramide bound to human serum albumin (HSA) to a limited extent and to human AAG to a greater extent indicating that AAG is the major binding protein for the drug in plasma.

The plasma protein binding of theophylline was measured in 21 patients with renal disease and 21 healthy age and sex matched controls. The percentage of theophylline unbound to plasma was greater in patients with nephrotic syndrome and in chronic renal failure than in controls. In nephrotic syndrome the impairment of drug binding mirrored the marked degree of hypoalbuminaemia seen in this condition but in chronic renal failure the impairment of protein binding was greater than would be expected from the plasma albumin concentration changes. The percentage of theophylline free in plasma in renal disease may be increased (by as much as 50%). Such changes should be taken into account in interpreting the relationship between total plasma theophylline concentration and drug effect in renal disease.

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