Effect of hemodialysis on propoxyphene and norpropoxyphene concentrations in blood of anephric patients*

Abstract

Our purpose was to determine whole-blood hemodialysis clearances and the effect of hemodialysis on blood propoxyphene concentrations and of its major metabolite, norpropoxyphene, in anephric patients under apparent steady-state conditions with respect to propoxyphene. Propoxyphene hydrochloride 130 mg was given orally every 8 hr for 7 doses to 4 patients. Blood propoxyphene and norpropoxyphene levels were determined repeatedly during the sixth dosing interval (before hemodialysis) and during the seventh dosing interval (during hemodialysis). There were no statistically significant differences in the areas under the blood level/time curves of propoxyphene and norporopoxyphene during the sixth and seventh dosing intervals, indicating that hemodialysis contributes negligible to their total clearance from the body. The low hemodialysis clearances of propoxyphene and norpropoxyphene were confirmed by direct in vivo determination of their hemodialyzer extraction ratios. Propoxyphene produces much higher propoxyphene plasma levels and higher as well as more persistent norpropoxyphene plasma levels in anephric patients than in normal subjects. In view of their substantive cumulation during repeated propoxyphene administration, their central nervous system and cardiac toxicity at high concentrations, their low hemodialysis clearance, and the apparent sensitivity of patients with renal failure to narcotics, propoxyphene should be used cautiously in anephric patients.