Propoxyphene and norpropoxyphene plasma concentrations in the anephric patient

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Abstract
The widely used analgesic propoxyphene is subject to extensive presystemic (first-pass) biotransformation after oral administration. There were indications that presystemic biotransformation of a drug may be less in anephric patients than in healthy subjects. Plasma concentrations of propoxyphene (a drug with dangerous adverse effects at high concentrations) and its major and pharmacologically active metabolite norphropoxyphene were compared in 7 anephric patients and 7 healthy subjects after oral administration of a 130-mg dose. Maximum propoxyphene concentrations were much higher (177 .+-. 16 vs. 81 .+-. 35 ng/ml, .hivin.x .+-. SD, P < 0.001), and areas under the concentration-time curve over 12 h were much larger (4310 .+-. 1520 vs. 2250 .+-. 1050 ng h/ml, P < 0.02) in the anephric patients than in the normal subjects. These differences were statistically significant even after normalization for dose per body weight. Norpropoxyphene concentrations were also higher and more persistent in the anephric patients. These differences, which appear to result from decreased presystemic biotransformation of propoxyphene and decreased elimination of norpropoxyphene, indicate that propoxyphene should be used cautiously and at reduced doses in patients with renal failure.