Plasma Codeine and Morphine Concentrations After a Single Oral Dose of Codeine Phosphate

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Abstract
Plasma concentrations of codeine and its O-demethylated metabolite morphine were determined, by a sensitive and specific high performance liquid chromatography (HPLC) method, following a single oral dose of 60 mg codeine phosphate. Ten healthy volunteers received a single dose of 60 mg codeine phosphate. The plasma concentrations were analyzed for codeine and morphine at the 0.5, 1, 3, and 6 hours postdosing. The mean peak codeine plasma concentrations and tmax (time to reach maximum plasma codeine concentrations) were 88.1 ng/mL and 1.2 hours. Mean maximum concentrations of metabolically produced morphine was 2.7 ± 0.6 ng/mL. The mean ratio of areas under the plasma concentration-time curves for morphine and codeine was 0.027. Thus, free morphine represented only about 2.7 ± 1.8% of the free codeine area in each case.