SOFT - TIAFT 1998 Scientific Session 2 Wednesday October 7, 1998
Click Picture Jonathan M. Oyler, Edward J. Cone, Robert E. Joseph, Jr.

Addiction Research Center, IRP, NIDA, NIH, Baltimore, MD, USA

Allegations of hydrocodone abuse have been made against individuals who were using physician prescribed codeine but claimed no illicit hydrocodone use. These allegations were based on the detection by gas chromatography-mass spectrometry (GC-MS) of low concentrations of hydrocodone (ca. 100 ng/mL) in urine samples containing high concentrations of codeine (>5000 ng/mL). We previously reported hydrocodone as a metabolite of codeine (Cone et. al., 1979) and recently had the opportunity to further investigate these findings. Five subjects in a controlled clinical study were orally administered 60 mg/70 kg/day and 120 mg/70 kg/day of codeine sulfate on separate days. Urine specimens were collected prior to and for 30 h following drug administration. In a separate study, a post-operative patient self-administered 960 mg of physician prescribed oral codeine phosphate/day, and urine specimens were collected on the third day of the dosing regimen. Unhydrolyzed urine specimens were analyzed by solid phase extraction followed by GC-MS. The two codeine formulations were also analyzed, and hydrocodone was not detected. In the controlled clinical study, codeine was detected in the first urine specimen following each drug administration; concentrations peaked rapidly (2-5 h) and ranged from 1,475-30,848 ng/mL. Hydrocodone was initially detected at 6-11 h following codeine administration and peaked (32-135 ng/mL) at 10-18 h. In specimens collected from the post-operative subject, hydrocodone and codeine concentrations ranged from 47-129 and 2,099-4,020 ng/mL, respectively, and appeared to have reached steady-state. These data indicate that hydrocodone is a minor metabolite of codeine and may be excreted in urine at concentrations as high as 5% of parent codeine. Consequently, the detection of minor amounts of hydrocodone with high concentrations of codeine in urine should not be interpreted as evidence of hydrocodone abuse.

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