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.