Changes

Pharmacokinetics for NSAIDs differ greatly between species, meaning that data from one species cannot be used to reliably calculate a dose for another. An example of such a variation is provided by phenylbutazone, which has zero-order kinetics in some species (including the dog), but first order kinetics in others. This means the half-life of this drug is variable and unpredictable.

Pharmacokinetics for NSAIDs differ greatly between species, meaning that data from one species cannot be used to reliably calculate a dose for another. An example of such a variation is provided by phenylbutazone, which has zero-order kinetics in some species (including the dog), but first order kinetics in others. This means the half-life of this drug is variable and unpredictable.

NSAIDs may be administered orally or parentally. As they are weak acids, NSAIDs are well absorbed following oral administration. The presence of food may, however, interfere with this absorption.

NSAIDs may be administered orally or parentally. As they are weak acids, NSAIDs are well absorbed following oral administration. The presence of food may, however, interfere with this absorption. Once absorbed, NSAIDs have a small apparent volume of distribution. In actuality, the magnitude is not that small; the drugs accumulate at sites of inflammation due to plasma protein escaping through leaky blood vessels in these locations. This is a good property - the drug reaches the areas where it is needed most.

 

The half-life of NSAIDs is often short, and so dosing is required every 4 to 6 hours. Despite this, the duration of action is quite long: although the drug leaves the plasma rapidly it remains bound to the COX enzyme for more extended periods.

Non-steroidal anti-inflammatory drugs have a high degree of plasma protein binding (approaching 99%). This means that other highly plasma protein-bound drugs with stronger binding affinities may displace NSAIDs from their binding. This would lead to an increase in circulating free drug levels and hence potential overdose. Although this is a theoretical risk, it has been demonstrated in relation to warfarin administration.

Non-steroidal anti-inflammatory drugs have a high degree of plasma protein binding (approaching 99%). This means that other highly plasma protein-bound drugs with stronger binding affinities may displace NSAIDs from their binding. This would lead to an increase in circulating free drug levels and hence potential overdose. Although this is a theoretical risk, it has been demonstrated in relation to warfarin administration.