Propranolol Dextropropoxyphene

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

A single-dose study has shown that the bioavailability of metoprolol is markedly increased by dextropropoxyphene and a case report supports these flndings. The bioavailability of propranolol is also increased, but to a lesser extent. 

Preliminary results of a study suggest that after taking dextropropoxyphene [dose not stated] for a day the bioavailability of a single 100-mg oral dose of metoprolol was increased by almost 260% and the total body clearance was reduced by 18% in healthy subjects. The bioavailability of a single 40-mg oral dose of propranolol was increased by about 70%. ... 

Dextropropoxyphene inhibits the metabolism of metoprolol and propranolol by the cytochrome P450 isoenzyme CYP2D6, which results in increased levels and therefore increased effects. Propranolol is probably affected to a lesser extent as it is also metabolised by CYP1A2. 

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