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By K K Jain MD

The full chemical name of tapentadol HCl is (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol hydrochloride.

Pharmacodynamics. Tapentadol is a centrally acting oral analgesic with a dual mechanism of action, combining mu-opioid receptor agonist and norepinephrine reuptake inhibition in a single molecule. Norepinephrine plays a role in the endogenous descending pain inhibitory system, and the analgesic efficacy of norepinephrine reuptake inhibitors has been shown in neuropathic pain.

Analgesic effect of tapentadol has been demonstrated in a wide range of animal models of pain with nociceptive and neuropathic components, and development of tolerance to its analgesic effect was twice as slow as that of morphine. Although tapentadol has a 50-fold lower binding affinity to mu-opioid receptor, its analgesic potency is only 2 to 3 times lower than that of morphine, indicating that the dual mode of action may result in an opiate-sparing effect (Tzschentke et al 2007).

Pharmacokinetics. A study investigated the absorption, metabolism, and excretion of tapentadol in humans using oral 3-[14C]-labeled tapentadol HCl (Terlinden et al 2007). Important findings were:

  • Drug absorption was rapid, reaching a maximum concentration of 2.45 microg-eq/mL in 1.25 to 1.5 hours.
  • The drug was present mainly in the form of conjugated metabolites.
  • Excretion was renal and complete within 5 days.

The absolute oral bioavailability of tapentadol is approximately 32%, which is comparable to that of morphine (Tzschentke et al 2006).