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

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Abstract
Whole-blood hemodialysis clearances and the effect of hemodialysis on blood propoxyphene [analgesic, PP] concentrations and of its major metabolite, norpropoxyphene [NP], was determined in anephric patients under apparent steady-state conditions with respect to PP. PP HC 130 mg was given orally every 8 h for 7 doses to 4 patients. Blood PP and NP levels were determined repeatedly during the 6th dosing interval (before hemodialysis) and during the 7th dosing interval (during hemodialysis). There were no statistically significant differences in the areas under the blood level/time curves of PP and NP during the 6th and 7th dosing intervals, indicating that hemodialysis contributes negligibly to their total clearance from the body. The low hemodialysis clearance of PP and NP were confirmed by direct in vivo determination of their hemodialyzer extraction ratios. PP produces much higher PP plasma levels and higher as well as more persistent NP plasma levels in anephric patients than in normal subjects. In view of their substantive cumulation during repeated PP administration, their CNS and cardiac toxicity at high concentrations, their low hemodialysis clearance and the apparent sensitivity of patients with renal failure to narcotics, PP should be used cautiously in anephric patients.