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American Clinical Solutions Releases Study "Tramadol - A Different Kind of Opioid"


American Clinical Solutions currently provides testing services for tramadol and tapentadol in both urine and oral fluid samples.

Sun City Center, FL, August 02, 2013 --(PR.com)-- Tramadol (Ultram) and tapentadol (Nucynta) are two unique members of the opioid family. Most of the opioids, either natural or synthetic ones, exert their analgesic effect by binding to opioid μ receptor in the central nervous system. Tramadol and tapentadol act not only as an agonist to opioid μ receptor, but also a serotonin and/or norepinephrine reuptake inhibitor (SNRI). Besides working as antidepressants, SNRIs like venlafaxine and duloxetine are also indicated for fibromyalgia and neuropathic pain of diabetes. The analgesic effects of tramadol and tapentadol may be attributed to a combined effect of these two pharmacological actions. Tramadol has an analgesic potency comparable to that of codeine. Upon entering human body, tramadol is metabolized by hepatic CYP450 enzymes, which leads to the formation of several metabolites. Among them, O-desmethyltramadol, formed through the action of CYP2D6, is of particular interest in that it has been proposed to possess analgesic potency several times greater than tramadol itself. Since the human CYP2D6 gene exhibits genetic polymorphism, a patient’s response to tramadol-mediated analgesic effects might well be predicated upon the genotype of the patient’s CYP2D6 gene. For example, poor metabolizers (about 5-15% of general population) might experience less than satisfactory pain-relieving effects. Tapentadol was developed based on the same concept of dual modes of action, in an attempt to avoid complex metabolism and variability in individual responses. Tapentadol, with a structure resembling that of tramadol, exhibits a stronger binding affinity towards the opioid μ receptor and also works as a norepinephrine reuptake inhibitor. More importantly, its major metabolite, tapentadol O-glucuronide, is pharmacologically inactive. Tapentadol's pharmacological effect is entirely dependent on the parent drug and not influenced by CYP2D6 polymorphism.

Although sharing some pharmacological properties, clinical indications of tramadol and tapentadol are different. Also, tapentadol, with a stronger “morphine-like” property, is currently regulated as a Schedule II controlled substance, while tramadmol is not. The major route for tramadol and tapentadol clearance is through urinary elimination. American Clinical Solutions currently provides testing services for tramadol and tapentadol in both urine and oral fluid samples. The detection window for tramadol in urine and oral fluid is about 1-3 days and 1.5 days, respectively; for tapentadol, about 1 day and 0.5 day, respectively. The concentrations of tramadol and tapentadol (free and conjugated) in urine, based on an internal study conducted by American Clinical Solutions from patients with known prescriptions, averaged 28176 ng/ml and 18516 ng/ml, respectively. Oral tramadol concentration was reported as 918.8 ng/ml according to a previous study. For physicians prescribing opioids for pain management, it should be noted that concentration levels of these two compounds in urine may appear to be alarmingly high in comparison with those of other commonly prescribed opioids. Dosing frequency (about 50-100 mg every 4-6 hours) and high dosages (daily dosage up to 400-600 mg) of these two medications may share in the cause for the unusually high levels in urine. The unique dual modes of action renders tramadol and tapentadol less additive and more suitable for managing chronic pain. In terms of side effects, seizure and serotonin syndrome – unusual side effects for the opioids but common for antidepressants – have been reported among patients using tramadol, especially when co-administered with TCAs and SSRIs. The inhibitory effect of tramadol on serotonin reuptake lowers the seizure threshold and permits the occurrence of serotonin syndrome. As a relatively new drug, there have not been enough reports on tapentadol toxicity.

Cheng Fang, MD., PH D., DABT | cheng.fang@americanclinicalsolutions.com

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American Clinical Solutions
Lauren Marshall
813-613-4533
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www.acslabtest.com

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