CLINICAL PHARMACOLOGY
Hydrocodone is a semisynthetic narcotic analgesicand antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. Theprecise mechanism of action of hydrocodone and other opiates is not known,although it is believed to relate to the existence of opiate receptors inthe central nervous system. In addition to analgesia, narcotics may producedrowsiness, changes in mood and mental clouding.
Theanalgesic action of acetaminophen involves peripheral influences, but thespecific mechanism is as yet undetermined. Antipyretic activity is mediatedthrough hypothalamic heat regulating centers. Acetaminophen inhibits prostaglandinsynthetase. Therapeutic doses of acetaminophen have negligible effects onthe cardiovascular or respiratory systems; however, toxic doses may causecirculatory failure and rapid, shallow breathing.
Pharmacokinetics
The behavior of the individual components is describedbelow.
Hydrocodone
Following a 10 mg oral dose of hydrocodone administeredto five adult male subjects, the mean peak concentration was 23.6 ± 5.2ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours and thehalf-life was determined to be 3.8 ± 0.3 hours. Hydrocodoneexhibits a complex pattern of metabolism including O-demethylation, N-demethylationand 6-keto reduction to the corresponding 6-α- and 6-β-hydroxy-metabolites. See OVERDOSAGE fortoxicity information.
Acetaminophen
Acetaminophen is rapidly absorbed from the gastrointestinaltract and is distributed throughout most body tissues. The plasma half-lifeis 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation)and subsequent renal excretion of metabolites. Approximately 85% of an oraldose appears in the urine within 24 hours of administration, most as the glucuronideconjugate, with small amounts of other conjugates and unchanged drug. See OVERDOSAGE for toxicity information.
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