I A study was made of the influence of hydralazine on the oral availability of a sustained release formulation of propranolol (Inderal LA®). Sustained release propranolol 160 mg was given orally either alone or in combination with oral hydralazine 25 mg on separate occasions to six healthy volunteers. Blood and urine samples were collected post-dosing over 34 h. 2 Peak concentrations of propranolol, time to peak and area under the plasma concentration-time curve (AUC) were not altered by co-administration of hydralazine with sustained release propranolol. 3 Similarly, there was no change in recovery of '4C-labelled propranolol and metabolites in those individuals to whom tracer label was given. 4 These results contrast with previous reports of marked interaction between the conventional formulation of propranolol and hydralazine or food. 5 Interactions were confirmed between hydralazine and conventional propranolol in three subjects who had been studied previously with sustained release propranolol. Analysis of metabolite profiles in one of these subjects established that the major metabolites do change under hydralazine stimulus. 6 These results indicate that substrate delivery rates may determine presystemic drug interactions, suggesting capacity limitations of hydroxylation processes or short-term flow redistribution following hydralazine, resulting in functional shunting past the hydroxylation enzymes. 7 These results exclude global or lasting enzyme inhibition by hydralazine or simple flow-sensitivity of presystemic clearance.
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