Context sensitive half-time: Opioids

Basic, Basic Sciences

Context sensitive half-time is the time required to decrease the plasma concentration of a drug by 50% after termination of an infusion. It takes into consideration the multi-compartmental model of pharmacokinetics. With an intravenous infusion, a drug is delivered directly to the plasma or central compartment and then distributes to tissues or peripheral compartments until equilibrium is reached. The extent that a drug redistributes to the tissues (also known as its volume of distribution) is determined by its physiochemical properties including lipid solubility, protein binding and ionized fraction. After termination of the infusion, the drug then redistributes from the peripheral compartments back to the central compartment where it is metabolized and excreted. With the exception of remifentanil, all opioids are metabolized in the liver via the cytochrome 450 system. Remifentanil is hydrolyzed in the plasma by non-specific plasma esterases.

The graph below displays the context sensitive half-time of common opioid infusions. The x axis describes total time of infusion and the y axis is the context sensitive halftime. Remifentanil- because of its rapid biotransformation in plasma and tissue, remifentanil has a short context sensitive half-life (~5 minutes), regardless of duration of infusion. Note that fentanyl’s context sensitive halftime increases significantly after 1hr of infusion. This is due to its very large volume of distribution and rapid redistribution. Alfentanil has a lower pKa than fentanyl resulting in more drug in the unionized form at physiologic pH and a smaller volume of distribution. Its context sensitive half-time peaks around 90 minutes and remains constant despite continued infusion.

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2019

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Author
Lindsay Brown, MD