06.04 Enhancing Elimination

The first example of a drug that it is possible to enhance elimination is paracetamol. A minor metabolite of paracetamol NAPQI is extremely toxic to the liver. Normally most of the paracetamol is conjugated and excreted (Figure 6.2). However, with high poisonous levels of paracetamol, the glutathione (GSH) becomes depleted, and NAPQI levels increase. N-Acetylcysteine provides a source of GSH to promote the elimination of NAPQI. GSH may also combine with NAPQI to reduce the toxicity to this compound, and hence to paracetamol (Figure 6.2).

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Figure 6.2 Promoting elimination of NAPQI (Copyright QUT, Sheila Doggrell)

Another way to promote the elimination of drugs is to increase their ionisation, as ionised drugs are readily excreted. For instance, aspirin is a weak acid and is readily reabsorbed from kidney tubule. Thus, aspirin is recycled and remains poisonous. Urine alkalinization with sodium bicarbonate increases the ionization of aspirin, and ionized aspirin is readily eliminated. The enhanced elimination of aspirin reduces its toxicity.