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Pharmacology: Pharmacodynamics: Tramadol is a centrally acting analgesic which possesses opioid agonist properties. Tramadol consists of two enantiomers, the (+)-isomer is predominantly active as an opioid with preferential activity for the μ-receptor. The (-)-isomer potentiates the analgesic effect of the (+)-isomer and is active as an inhibitor of noradrenaline and serotonin uptake thereby modifying the transmission of pain impulses.
Tramadol also has an antitussive action. At the recommended dosages, the effects of tramadol given orally on the respiratory and cardiovascular systems appear to be clinically insignificant. The potency of tramadol is reported to be 1/10th to 1/6th that of morphine.
Pharmacokinetics: General: The mean absolute bioavailability after intramuscular administration was found to be 100%.
The distribution of tramadol following intravenous administration is rapid and in two phases with different half-lives of 0.31 ± 0.17 hours (initial rapid phase) and 1.7 ± 0.4 hours (slower phase) respectively.
After intravenous administration of 100 mg tramadol, the serum concentration was 613 ± 221 ng/ml at 15 minutes post dosing and 409 ± 79 ng/ml at 2 hours post dosing. Tramadol has a high tissue affinity with an apparent volume of distribution of 203 L after intravenous dosing in healthy volunteers.
Tramadol undergoes hepatic metabolism with approximately 85% of an intravenous dose being metabolised in young healthy volunteers. In humans tramadol is mainly metabolised by means of N- and O-demethylation and conjugation of the O-demethylation products with glucuronic acid. Only O-desmethyltramadol is pharmacologically active. There are considerable interindividual quantitative differences between the other metabolites. So far, eleven metabolites have been found in the urine. Animal experiments have shown that O-desmethyltramadol is more potent than the parent substance by the factor 2-4. Its half-life t½β (6 healthy volunteers) is 7.9 h (range 5.4-9.6 h) and is approximately that of tramadol.
The inhibition of one or both cytochrome P450 isoenzymes, CYP3A4 and CYP2D6 involved in the metabolism of tramadol, may affect the plasma concentration of tramadol or its active metabolite.
Tramadol is essentially excreted via the kidneys. The mean elimination half-life of tramadol following intravenous administration is 5-6 hours. Total clearance of tramadol was 28.0 L/h following intravenous administration.
