To  :  Becky
Re  :  Pharmacokinetics of Radioconstrast agents

>The drug is gadoteridol (ProHance).  "The pharmacokinetics of intravenously
>administered gadoteridol in normal subjects conforms to a two-compartment
>open model with mean distribution and elimination half-lives (reported as
>mean +/- SD) of about 0.20 +/- 0.04 hours and 1.57 +/- 0.08 hours,
>respectively."  Going by 5 half-lives, it seems that 10 hrs. at the most
>ought to be okay for elimination, but what does "two-compartment" mean?

>"Gadoteridol is eliminated in the urine with 94.4 +/- 4.8% (mean +/- SD) of
>the dose excreted within 24 hours post-injection."



The human body is divided into multiple "compartments" within which
drugs penetrate, stay for awhile, and then ultimately leave. Valium for
instance, enters the plasma compartment, rapidly penetrates the brain
complartment.  It stay there in high concentrations for a few minutes,
then rapidly distributes to other compartments such as fat and skeletal
muscle.   Such compartments include the blood, fat tissues, liver,
heart, muscle, brain, etc. etc., etc...

The drug may have a unique and different half-life in each compartment
individually.  It may have a half-life of 20 minutes in the plasma,  but
20 hours in the adipose tissue (two compartment).  This is not
uncommon.  The mean distribution half-life describes the time(in
half-lives) required for it to distribute completely to all tissues, but
most generally describes the time for it to leave the plasma for other
compartments.

The most important half-life however, is the "Elimination Half-life"
which describes the time required for one half of the drug to be
completely eliminated from most compartments.  In the above example,
the 1.57 hour half-life is the time required for the human body to
elimate approximately one-half of the drug.  You are correct in that
after approximately 5 half-lives,  97.5% of the drug is eliminated,  but
a little still remains and slowly leaks out.  This is where the second
statement comes in.  The majority of the drug is elinated very quickly,
but other deeper compartments continue to leak it out over a prolonged
period.  During this time,  the plasma levels are probably so low, that
they are undetectible.

The radiocontrast agents by nature are primarily restricted to the
plasma compartment, and penetrate other compartments minimally.  Hence
they almost all have very brief half-lives.  Because they cannot leave
the vascular comparment very well,  they also probably cannot penetrate
milk very well.  We still have no data on this but I would guess they
penetrate milk minimally.

Further,  as a class,  their oral bioavailability is low to nil.  I
generally recommend that moms pump and dump for at most four or five
half-lives before restarting breastfeeding.  This is probably not even
necessary,  but I'm rather cautious and this satisfys most clinicians
when they find out the average half-life is about 30-50 minutes and most
moms don't consider this brief interruption troublesome.

I hope this helps,  as pharmacokinetics is a powerful tool in
understanding how drugs work.   Isn't pharmacokinetics fun !!!!

Regards

Tom Hale, Ph.D.

PS:  I'll be gone a few days to Syracuse NY for lectures.