At high doses or in sensitive patients, HC may produce dose-related respiratory depression by acting directly on the brain stem respiratory center. Hydrocodone (HC) is a semi-synthetic opioid that is orally active as an antitussive and an analgesic medication for the treatment of moderate to moderately severe pain. These data suggest that drug-testing requirements for HC should include a hydrolysis step and a test for HM. Creatinine corrections of HC urinary data had variable effects of lowering or raising concentrations. Creatinine and SG measures were highly correlated. Some specimens did not contain HC, but most contained NHC, thereby facilitating interpretation that HC was the administered drug. At a cutoff concentration of 50 ng/mL, detection times were ∼28 h for HC, 40 h for NHC, 26 h for HM and 16 h for DHC. Only HM was excreted extensively as a conjugated metabolite. Peak hydrolyzed concentrations were in the order: NHC > HC > HM > DHC. Peak concentrations of HC and metabolites occurred at 3–9 h. HC and norhydrocodone (NHC) appeared within 2 h followed by HM and DHC. All specimens were also analyzed for creatinine and specific gravity (SG). Urine specimens were collected at timed intervals for up to 52 h and analyzed by LC–MS-MS (limit of quantitation = 50 ng/mL) with and without enzymatic hydrolysis. Twelve healthy, drug-free, adults were administered a single, oral 20 mg immediate-release dose of HC in a controlled clinical setting. This study characterized the disposition of HC in human urine. Currently, there is interest in including HC and HM in the federal workplace drug-testing programs. Interpretation of urine tests for HC is complicated by its metabolism to two metabolites, hydromorphone (HM) and dihydrocodeine (DHC), which are also available commercially and are misused. Hydrocodone (HC) is a highly misused prescription drugs in the USA.
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