Re: Re: INFO - More on Arava (leflunomide) persistence/clearance

[Guest guest]

Sierra,

Assuming many things (for example, one assumption I'll make is that you were

taking 20 mg per day - time is a more important factor here anyway; another

is that we don't care that you probably didn't reach a steady state yet -

that would take about five half-lives), it's generally accepted that, for a

great many medications, ROUGHLY 97% of a given drug is eliminated after 5

half-lives.

http://www.boomer.org/c/p1/Ch04/Ch0411.html

The problem is: which half-life value am I going to use to try to estimate

your situation?

Although it's stated by the manufacturer (Aventis) that the half-life of

Arava averages approximately two weeks, Aventis gives a range of between 1

and 4 weeks:

http://www.medsafe.govt.nz/Profs/Datasheet/a/Aravatab.htm

A few other sources list 6 weeks.

This article reports on the half-life of the active metabolite of

leflunomide:

" Without cholestyramine, half-lives of up to 96 days have been found

(population kinetics analysis). Thus, it may take up to 2 years to reach

plasma active metabolite levels of <0.02 mg/ml due to individual variations

in drug clearance. "

http://teratology.org/updates/63pg106.pdf

96 days! That's a half-life of almost 14 weeks. It might be unusual, but it

serves to illustrate that there is wide variability in the observed

half-life values.

So, if, for you and your circumstances, the half-life is 1 week, then 97% of

the Arava is eliminated after 5 weeks. If, for you, the half-life is two

weeks, then 50% of the Arava is gone after two weeks, 97% is gone after 10

weeks. If, for you, the half-life is around 4 weeks, then 97% of the Arava

would be eliminated after 20 weeks. A half-life of 6 weeks would mean that

97% is gone after 30 weeks. A half-life of 14 weeks would mean that 97% is

gone after 70 weeks.

Also, to make things a bit more concrete, you can imagine, for the sake of

simplicity, that you took all 420 mg (20 mg per days x 21 days) on one day

and count down from there. Best case (half-life of 1 week): 97% of 420 mg

(407 mg) is gone after 5 weeks (13 mg remains). Worst case (half-life of 14

weeks): 97% of 420 mg is gone after 70 weeks (and you still have 210 mg in

your system after 14 weeks). Manufacturer's guess (2-week half-life): you

have 210 mg in your system after 2 weeks, you have 105 mg in your system

after 4 weeks, you have 52.5 or or mg left after 6 weeks.

It gets more complicated if you consider that the first and last dose are

three weeks apart. But you probably get the basic idea.

That's the best I can do since there are so many individual variations,

because I had to make some significant assumptions, and I am not sure of the

half-life. It's very hard to know!

Bottom line: It's not unreasonable to think that the Arava could still be

helping you.

Not an MD

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org

[ ] Re: INFO - More on Arava (leflunomide)

persistence/clearance

> Do you know what this would translate to for a 3 week use--no loading

> dose. (Can't recall the dose, but it was the standard given.)

>

> Sierra

>

>

>

>>

>> Clinical Geriatrics

>> " Management of Rheumatoid Arthritis in the Elderly "

>>

>>

>> Excerpt:

>>

>> " Leflunomide is a pro-drug that undergoes hepatic metabolism in the

> liver to

>> an active metabolite, A77 1726, two-thirds of which is excreted by

> the gut

>> and one-third by the kidney. The half-life of leflunomide is rather

> long,

>> about 15 days. In addition, the drug undergoes continuous

> enterohepatic

>> recirculation. Leflunomide levels will therefore remain for many

> months

>> after the medication is stopped. The drug can be efficiently

> removed from

>> circulation with the addition of the resin cholestyramine, which

> binds

>> leflunomide in the gut, causing elimination in the stool. "

>>

>>

>> http://www.hmpcommunications.com/cg/displayArticle.cfm?

> articleID=cgac547

>>

>>

>>

>>