Effect of Anticonvulsants on Serum Protein Binding of ¹⁴C -Diazepam

Abstract

Serum protein binding of ¹⁴C-diazepam in normal serum and the effect of anticonvulsants were investigated with the centrifugation technique. ¹⁴C-diazepam was bound by 98.1 per cent in normal human serum.
At concentrations of 500, 750 and 1, 000μmol/l sodium valproate, the amount of the unbound ¹⁴C-diazepam was increased from 1.75±0.42%(mean±SD, n=6) to 3.51±0.71%(P<0.001), 3.96±0.19%(P<0.001) and to 4.05±0.75%(P<0.001), respectively. Further studies indicated that sodium valproate inhibited competitively serum protein binding of ¹⁴C-diazepam. At therapeutic concentrations, phenytoin, phenobarbital and carbamazepine had no effects on serum protein binding of ¹⁴C-diazepam.