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Re: Tegretol, Dilantin..... Ritch

Posted by ed_uk on March 22, 2005, at 10:29:33

In reply to Re: Tegretol, Dilantin..... ed_uk, posted by Ritch on March 22, 2005, at 10:12:29

Hi Mitch!

>I was just wondering about the specific "problem" of serum protein binding by medications and how this presents an entirely different "interaction" phenomenon from the kind you typically read about regarding liver enzymes and elimination.

Here is a summary from the BNF....

To a variable extent most drugs are loosely bound to plasma proteins. Protein-binding sites are non-specific and one drug can displace another thereby increasing its proportion free to diffuse from plasma to its site of action. This only produces a detectable increase in effect if it is an extensively bound drug (more than 90%) that is not widely distributed throughout the body. Even so displacement rarely produces more than transient potentiation because this increased concentration of free drug results in an increased rate of elimination.

Displacement from protein binding plays a part in the potentiation of warfarin by sulphonamides, and tolbutamide but the importance of these interactions is due mainly to the fact that warfarin metabolism is also inhibited.'

'Plasma protein binding (of Lamictal) is 55% and none of the metabolites are active as anticonvulsants.'

For Depakote, plasma protein binding is about 90%

>From what I remember I think the serum protein binding is what creates a significant interaction between Depakote and Lamictal.

Although the mechanism of this iinteraction is not fully understood, it is thought that the two drugs may compete for glucuronidation by the liver, this may result in decreased lamotrigine clearance. I'm not sure whether the interaction involves plasma protein binding.

> Thanks for your help!

LOL- I'm not sure that I've been that helpful :-)





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