CLINICAL PHARMACOLOGY
Clinical trials have proven hydrocodone bitartrate to be an effective antitussive agent which is pharmacologically 2 to 8 times as potent as codeine. At equi-effective doses, its sedative action is greater than codeine. The precise mechanism of action of hydrocodone and other opiates is not known, however, hydrocodone is believed to act by directly depressing the cough center. In excessive doses hydrocodone, like other opium derivatives, can depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system is insignificant. The constipation effects of hydrocodone are much weaker than that of morphine and no stronger than that of codeine. Hydrocodone can produce miosis, euphoria, physical and psychological dependence. At therapeutic antitussive doses, it does exert analgesic effects. Following a 10 mg oral dose of hydrocodone administered to five male human subjects, the mean peak concentration was 23.6 ± 5.2 ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours
and half-life was determined to be 3.8 ± 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-(alpha)- and 6-(beta)-hydroxymetabolites.
The exact mechanism of action is not established but guaifenesin is believed to act by stimulating receptors in the gastric mucosa that initiates a reflex secretion of respiratory tract fluid, thereby increasing the volume and decreasing the viscosity of bronchial secretions. Studies with guaifenesin indicate that it is rapidly absorbed from the gastrointestinal tract and has a half-life of one hour.
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