Pethidine binding to blood cells and plasma proteins in old and young subjects

The distribution of 3H-pethidine in whole blood was compared in old (63-86 years; n = 11) and young (19-25 years, n = 12) subjects using equilibrium dialysis. The plasma protein binding was 52.7 +/- 3.3% (mean +/- SD) in the old subjects and 51.8 +/- 3.1% in the young: the difference was not statistically significant. Studies on isolated plasma protein fractions showed that the main pethidine-binding protein was alpha 1-acid glycoprotein. Accordingly, the degree of pethidine binding is likely to be affected by inflammatory disease rather than by age. The distribution of pethidine to blood cells showed no age-related difference; the ratio between whole blood and plasma concentrations was 0.99 in old and 0.98 in young subjects. In whole blood from old and young subjects, 43% and 41% of pethidine was present in erythrocytes, 27% and 26% in plasma water whereas 30% and 29% was bound to plasma proteins. The mean ratio between pethidine in cells and plasma water (2.01) indicates binding of the drug in or on the blood cells. These in vitro results do not support the previous theory that a decrease in intracellular pethidine distribution in old age was the reason for the reported higher plasma levels. A slower elimination rate remains the most likely explanation for the increased plasma concentration of pethidine in old patients.