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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Propoxyphene and norpropoxyphene plasma concentrations after oral propoxyphene in cirrhotic patients with and without surgically constructed portacaval shunt.

Plasma concentrations of propoxyphene and its major metabolite, norpropoxyphene, were determined over at least 12 hr after oral administration of 130 mg dextropropoxyphene hydrochloride to eight men with hepatic cirrhosis, of whom four had a surgically constructed portacaval shunt, and to seven healthy men. Propoxphene concentrations were appreciably higher and norpropoxyphene concentrations were much lower in the patients than in the normal subjects. The ratio of areas under the plasma concentration-time curve from 0 to 12 hr, norpropoxyphene: propoxyphene, was 0.70 +/- 0.46 (x +/SD) in patients and 3.94 +/ 0.83 in normal subjects. A similar decrease in this ratio was observed previously in otherwise healthy dogs after surgical construction of portacaval shunt when propoxyphene was given orally, but not after intravenous injection of the drug. A woman with portacaval shunt and essentially complete renal failure was also studied; she exhibited the highest propoxyphene peak concentration in this investigation and had no detectable norpropoxyphene in plasma. Most of the patients, unlike the normal subjects, experienced considerable sedation after propoxyphene. These results are probably due to increase systemic availability of orally administered propoxyphene in patients with hepatic cirrhosis and possibly to increased receptor response to the drug by these patients. It is concluded that propoxyphene should be administered cautiously and in reduced doses to patients with hepatic dysfunction.[1]


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