Changes

==Pharmacokinetic Considerations==

==Pharmacokinetic Considerations==

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.  

 

Some drugs may display zero-order kinetics, i.e. the rate of metabolism of the drug is constant and does not vary with dose. This is the case for phenylbutazone in the dog and salicylate in the cat.

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.

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.

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.

NSAIDs primarily undergo hepatic metabolism, but there is some excretion of unaltered drug in the urine, which is enhanced by an alkaline pH. This is an example of ion trapping: since NSAIDs are weak acids, there is a greater degree of ionisation in an alkaline environment, making it more difficult for the drug to cross membranes and escape back to the circulation.  

NSAIDs primarily undergo hepatic metabolism and excretion, which is slow before six weeks of age. Some metabolites such as oxyphenbutazone and salicylate are active.  There is some excretion of unaltered drug in the urine, which is enhanced by an alkaline pH. This is an example of ion trapping: since NSAIDs are weak acids, there is a greater degree of ionisation in an alkaline environment, making it more difficult for the drug to cross membranes and escape back to the circulation.  

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.