Panadol Extend Mechanism of Action

Pharmacology: Pain is a very common experience and analgesic drugs such as paracetamol plays an important role in providing general pain relief for both acute and chronic pain. Paracetamol is widely recommended as the initial drug of choice for the treatment of mild to moderate musculoskeletal pain and symptomatic osteoarthritis as it is regarded as having a more acceptable safety profile in chronic use than nonsteroidal anti-inflammatory drugs (NSAIDs).
Panadol Extend provides analgesic action via its inhibition activity on the central prostaglandin synthetase and its antipyretic action is thought to be due to selective inhibition of prostaglandin synthesis in the central nervous system (CNS).
Panadol Extend is readily absorbed from the upper small intestine, has absolute oral bioavailability (70-90%) and is extensively metabolized in the liver.
Pharmacokinetics: Panadol Extend formulation consists of a bilayer tablet containing 665 mg of paracetamol: One layer containing an immediate-release (IR) formulation and providing 31% of the total dose and a 2nd layer containing a sustained release (SR) formulation that provides the remaining 69% of the total dose.
Pharmacokinetics of Panadol Extend have been investigated in 2 pivotal biostudies. In the First study, Panadol Extend and Panadol tablets were compared in fed and fasted volunteers. Both were bioequivalent with respect to dose-corrected AUC_(0-t) and AUC_(0-inf) in both fed and fasted states. The bioavailability of paracetamol from Panadol Extend is not affected by food thus indicating that the formulation can be taken with or without food.
In the Second study, where Panadol Extend was again compared with Panadol; Panadol Extend showed a clear pattern of controlled release of paracetamol, and the formulations were bioequivalent based on the comparison of AUCs for the final 24 hours of the 48-hour dosing period. This shows that there is no additional accumulation of paracetamol from the Panadol Extend formulation. Besides that, steadier concentrations of paracetamol were achieved with Panadol Extend. Thus, Panadol Extend may be particularly appropriate for patients who require repeat doses as it maintains a continuous therapeutic effect when taken every 8 hours (2 x 665 mg tablets per dose).