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Ibute independently to the overall analgesic profile of tramadol. The analgesic effect is dose-dependant but the relationship between serum concentrations and analgesic effect varies considerably between individuals. In one study, the median serum concentration of tramadol required for effective post-operative analgesia was 300 ng mL, with individual values ranging from 20 to 990 ng mL. Apart from analgesia, tramadol may produce other symptoms similar to that of opioids including; dizziness, somnolence, nausea, constipation, sweating and pruritus. However, tramadol causes significantly less respiratory depression than morphine. In contrast to morphine, tramadol has not been shown to cause histamine release. At therapeutic doses, tramadol has no clinically significant effect on heart rate, left ventricular function or cardiac index. Orthostatic changes in blood pressure have been observed. Pharmacokinetics Absorption Tramadol is rapidly and almost completely absorbed after oral administ
tramadol hydrochloride capsules 50mg Ation and glucuronidation or sulfation in the liver. Only M1 is pharmacologically active. Production of M1 is dependent on the CYP2D6 isoenzyme of cytochrome P450. Excretion Tramadol and its metabolites are excreted mainly via the renal route tramadol hydrochloride capsules 50mg, with a cumulative renal excretion (tramadol and metabolites) of approximately 95%. The proportion of unchanged tramadol excreted by this route is greater in elderly subjects (34.9% and 23% respectively of the dose administered by the intravenous and oral route in the preceding study) than in young subjects (13.6% and 10.1% of the dose); mean doses obtained for all of the studies including those using other formulations tramadol hydrochloride capsules 50mg.
tramadol hydrochloride capsules 50mg . Biliary excretion was shown to be of little importance. In a study of cholecystectomised patients tramadol hydrochloride capsules 50mg, the cumulative biliary excretion of unchanged tramadol proved to be 240 times lower than its renal excretion and this relationship was 1 390 and 1 70 for the M1 and M1 conjugated metabolites respectively. The half-life of tramadol is in the order of 5-7 hours in young adults tramadol hydrochloride capsules 50mg, with relatively modest coefficients of variation. Following repeated administration tramadol hydrochloride capsules 50mg, the increase in bioavailability is accompanied by an increase in renal excretion. The half-life of M1 corresponds approximately to that of unchanged tramadol (6-8 hours). Pharmacokinetics in patients with hepatic or renal impairment Elimination of tramadol and M1 is impaired in patients with hepatic or renal impairment (see WARNINGS AND PRECAUTIONS). In patients with hepatic impairment tramadol hydrochloride capsules 50mg, the mean half-life of tramadol was found to be 13 h (range up to 19 h ) tramadol hydrochloride capsules 50mg, and the mean half-life of M1 was 19 h (range up to 36 h). In patients with severe renal impairment (creatinine clearance < 5mL min) the mean half-life of tramadol was 11 h (range up to 20 h) tramadol hydrochloride capsules 50mg, and the mean half life of M1 was 17 h (range up to 43 h). Pharmacokinetics in the elderly In the elderly (age over 75 years) tramadol hydrochloride capsules 50mg, the volume of distribution of tramadol is decreased by 25% and clearance is decreased .
tramadol hydrochloride capsules 50mg hepatic or renal impairment Elimination of tramadol and M1 is impaired in patients with hepatic or renal impairment (see WARNINGS AND PRECAUTIONS). In patients with hepatic impairment tramadol hydrochloride capsules 50mg, the mean half-life of tramadol was found to be 13 h (range up to 19 h ) tramadol hydrochloride capsules 50mg, and the mean half-life of M1 was 19 h (range up to 36 h). In patients with severe renal impairment (creatinine clearance < 5mL min) the mean half-life of tramadol was 11 h (range up to 20 h) tramadol hydrochloride capsules 50mg, and the mean half life of M1 was 17 h (range up to 43 h). Pharmacokinetics in the elderly In the elderly (age over 75 years) tramadol hydrochloride capsules 50mg, the volume of distribution of tramadol is decreased by 25% and clearance is decreased b.
tramadol hydrochloride capsules 50mg 
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| tramadol hydrochloride capsules 50mg
Ough (ng mL) - - 156 + 87 265 + 67 Distribution Tramadol is rapidly distributed in the body, with a volume of distribution of 2 - 3 L kg in young adults. The volume of distribution is reduced by about 25% in those aged over 75 years. Plasma protein binding is about 20% and is independent of concentration up to 10 & 956;g mL. Saturation of plasma protein binding occurs only at concentrations outside the clinically relevant range. Tramadol crosses the placental and blood-brain barriers. Very small amounts of tramadol and M1 are found in breast milk (0.1% and 0.02% respectively, of the administered dose). Metabolism Tramadol is extensively metabolised after oral administration. The major metabolic pathways appear to be N - and O -demethylation and glucuronidation or sulfation in the liver. Only O -desmethyltramadol (M1) is pharmacologically active. Production of M1 is dependent on the CYP2D6 isoenzyme of cytochrome P450. Patients who metabolise drugs poorly via CYP2D6 may obtain reduced b
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