I have 2 concentration time curves of a subcut drug implant. the first group has a peak around the 50 day mark where as the second group does not. Both groups received the same implant by the same surgical procedure. If the AUC for group 1 (1018 ng.days.ml-1) is larger than group 2 (800.9 ng.day.ml-1) over the same amount of time, can you assume that the implant in group 2 has more drug left in it compared to group 1?
Hi
If AUC from both implants are different (if I correctly understand load/dose is the same in both groups and there was no any other BIAS in the study) as you said its mean bioavailability of the drug from both is different. In your case looks the second group gets an implant which not released the whole drug substance into the bloodstream (of course if it's a synthetic drug, not biologics).
If you see a peak after 50 days it's valuable to calculate absorption rate constant - Ka (in fact its rate describing the rate of drug release). If your Ka is different for both groups you can be sure that differences in AUC are a consequence of differences in drug delivery rate from your implant. So if you have significant differences between implants then you can see differences in AUC and Ka. Of course, probably in your case Kel (elimination rate constant) will be affected by the prolonged absorption-long release process please remember about it (flip-flop phenomenon could be visible).
Another valuable comparison in your case will be mean residence time calculation (MRT) should be the same if both PK profiles represent the same phases (slopes, highest, amounts, moments - SHAM).
Best regards
Tomasz
You appear to be describing group means for 2 sample groups. Probability in play, one would not expect identical means from two groups. What is the variance, have you done comparative statistics to be able to state that these are statistically different and if they aren't then you can calculate means for the entire population of samples to report as your descriptive statistics. As to why they are different, the previous explanation was good and focused on the variabillity of the drug release from the implant. The surgical procedures may have been identical but people are not. Differences in local blood supply, fat composition, electrolyte values etc will result in variable bioavailability even if the device delivery is consistent. Further there will be different metabolizers among people and given the long duration of drug delivery this can make blood levels variable amongst people. In research it is better to investigate than to assume, if you want to answer the drug retention question, then have the implants removed and analyzed for drug content. However, even if different it does not rule continued variability in people since those devices typically deliver based on osmotic uptake of water to force the drug out, so again variability in the SC environment will produce variable delivery which when mixed with variable bioavailability means all you can do is gain large sample sizes and provide descriptive statistics to characterize the drug delivery to populations.
Hello.
While the AUC is proportional to the dose absorbed, that is not the only proportionality factor. The AUC is also related to the clearance, which is physiological and should not be assumed to be the same among subjects or populations. (For instance, AUC = F x Dose/Clearance, where F is the fraction absorbed.) As a result, the dose lost from the implant can't be assumed to be proportional to the AUCs
(By the way, this does not contradict looking at other factors as well.)
Hope this helps!
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology
- Pharmaceuticals
- Drugs