Is tapentadol a potential Trojan horse in the post dextropropoxyphene era in India?

Widespread within the U.S., pain is related to significant adverse economic, clinical, and quality-of-life outcomes: from 15% to twenty of patients within the U.S. experience acute pain, up to 75% of patients experience pain after surgery, and 68 million people have chronic pain annually .1,2 Uncontrolled pain is that the leading explanation for disability; it’s going to also delay patient recovery from surgery, increase risk of life-threatening events (such as deep-vein thrombosis or myocardial infarction), and cause the event of chronic pain.1 For back pain alone, total health care expenditures in 2004 and 2005 were estimated at $85 billion to $100 billion.3

Current pharmacological treatment options commonly used for moderate-to-severe pain include anticonvulsants, antidepressants, nonsteroidal anti-inflammatory drug agents (NSAIDs), tramadol (Ul-tram, PriCara), and opioids. 

Anticonvulsants and antidepressants are related to intolerable adverse effects (AEs) and various drug interactions, and successful analgesia is achieved in just 50% of patients with neuropathic pain.2 NSAIDs are effective for managing chronic pain, but their use is restricted by their gastrointestinal (GI) and cardiovascular toxicity, adverse renal effects, and an increased risk of bleeding.

Opioids are highly effective for acute and chronic pain, but their use is restricted by nausea, vomiting, constipation, and sedation, also because of the possibility of addiction or dependence. Tramadol is a beautiful alternative to opioids, but it’s subject to genetic polymorphism because it’s metabolized by cytochrome P-450 (CYP) 2D6, features a neurotoxic metabolite, and should predispose patients to serotonin syndrome.4

Despite the supply of those numerous options, pain continues to be under-treated,2 indicating a requirement for a potent analgesic with a coffee side-effect profile. tapentadol for sale HCl immediate release (IR) (Nucynta, PriCara), a centrally acting analgesic, was approved by the FDA on November 20, 2008, for the relief of moderate-to-severe acute pain. A long-acting formulation is being investigated.

Tapentadol produces its pharmacological effect by mu-opioid agonism and norepinephrine reuptake inhibition5,6 and is very selective for the mu-opioid receptor. By comparison, the drug’s binding to the kappa-opioid receptor and delta-opioid receptor is 10-fold less potent, and binding to the ORL1 receptor is 1,000-fold less potent. Tolerance is feasible but appears to be delayed.6

Tapentadol is rapidly absorbed, with a maximum serum concentration (Cmax) typically observed between 1.25 and 1.5 hours.7 Dose-proportional increases within the Cmax and area-under-the-curve (AUC) values of tapentadol are observed above the 50- to 150-mg dose range, suggesting linear pharmacokinetics. Tapentadol’s AUC and Cmax have increased by 25% and 16%, respectively, following a high-fat, high-calorie meal.

The mean absolute bioavailability after one dose is 32% as a result of the medication’s extensive first-pass metabolism. Tapentadol is cosmopolitan throughout the body, with a volume of distribution of roughly 540 liters.5 Plasma binding is low and has been reported at approximately 20%.8

Tapentadol is primarily and extensively (70%) metabolized by glucuron-idation by the UGT1A9 and UGT2B7 enzymes to inactive metabolites. Phase 1 metabolites include N-desmethyl tapentadol (13%) as a results of buy flexeril online legally metabolism by CYP 2C9 and 2C19, and hydroxy tapentadol (2%), as a results of metabolism by CYP 2D6, which are further metabolized by conjugation.7 The metabolites of tapentadol don’t contribute to the drug’s analgesic activity.5

Tapentadol is excreted primarily by the renal system 69% is excreted within the sort of conjugates, 27% as other metabolites, and three as unchanged drug. Fecal clearance accounts for 1% of tapentadol’s elimination.

The apparent half-life of tapentadol following oral administration is 3.93 hours, and quite 95% of the drug is excreted within 24 hours of dosing.7 the entire tapentadol clearance is 1,530 ± 177 mL/minute.5

The pharmacokinetic properties of tapentadol don’t appear to be suffering from renal impairment. Moderate hepatic impairment leads to decreased metabolism of tapentadol, leading to higher exposures and serum tapentadol levels. The pharmacokinetic parameters of tapentadol haven’t been evaluated in patients with severe hepatic impairment.