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Eur J Clin Pharmacol. 1983;25(3):419-24.

Pharmacokinetics of intravenous and oral dihydrocodeine and its acid metabolites.


Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6 h-1.8 h. The mean half-lives varied between 3.3 h-4.5 h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12-34%). The peak levels of the acidic metabolites occurred between 1.8 h-2.0 h after oral administration and 2.2 h-2.5 h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.

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