PROTEIN-BINDING CHARACTERIZATION OF PETHIDINE AND NORPETHIDINE AND LACK OF INTERETHNIC VARIABILITY

Using dialysis, incubation experiments and gas liquid chromatographic method, we studied the binding of pethidine (P) and norpethidine (N) to various protein components and plasma of both healthy volunteers and patients. The displacement interactions and interethnic variations of P and N were also examined. The (mean +/- S.D.) plasma protein binding ranged from 72 +/- 2.8 to 43 +/- 2.7% and from 57 +/- 3.0 to 27 +/- 3.9%, respectively, at various concentrations of P and N. Protein concentration-dependent binding was observed in P and N with albumin and alpha-1-acid glycoprotein. Albumin was found to be the major protein component in the binding, whereas gamma-globin contributed smaller binding activity than other protein fractions at therapeutic concentration of the drugs. The binding affinities of P were comparatively higher than N in all circumstances. The % P bound was almost constant with respect to various concentrations of N and vice-versa, indicating these two compounds exhibited no displacement action on the binding site to one another. The (mean +/- S.D.) % P bound for Caucasian, Chinese and Nepalese patients were 59 +/- 15%, 55 +/- 10% and 58 +/- 12%, respectively, at near 0.1-mu-g/ml of P, implying the absence of interethnic variation in P protein binding.