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In vitro drug interaction studies in human liver microsomes indicates that inhibitors of CYP2D6 such as fluoxetine and its metabolite norfluoxetine, amitriptyline and quinidine in-hibit the metabolism of tramadol to various degrees. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Concomitant use of SEROTONIN re-uptake INHIBITORS and MAO IN-HIBITORS may enhance the risk of adverse events, in-cluding seizure (see WARNINGS) and serotonin syndrome.
Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways:
a) conjugation with glucuronide;
b) conjugation with sulfate; and
c) oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a re-active intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appears to be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways. In adults, the majority of acetaminophen is conjugated with glucuronic acid and, to a lesser extent, with sulfate. These glucuronide-, sulfate-, and glutathione-derived metabolites lack biologic activity. In premature infants, newborns, and young infants, the sulfate conjugate predominates. Text Continues Below
Elimination Tramadol is eliminated primarily through metabolism by the liver and the metabolites are eliminated primarily by the kidneys. The plasma elimination half-lives of racemic tramadol and M1 are approximately 5-6 and 7 hours, respectively, after administration of ULTRACET. The apparent plasma elimination half-life of racemic tramadol increased to 7-9 hours upon multiple dosing of ULTRACET. The half-life of acetaminophen is about 2 to 3 hours in adults. It is somewhat shorter in children and somewhat longer in neonates and in cirrhotic patients. Acetaminophen is eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner. Less than 9% of acetaminophen is excreted unchanged in the urine. Page: << Prev | 1 | 2 | 3 | 4 | 5 | Next >>
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