Bioequivalence and Bioavailability Forum

Hi ssussu,

❝ ❝ […] Did you use an infusion pump or an infusion bottle / drip chamber?

❝

❝ Yes, the burble is extruded by squeezing the tube to float the burble up from the liquid surface of the tube, like this

❝ [image]

❝ so, the dose is not lost.

❝

❝ ❝ ❝ ❝ 2. only if you lost nothing […] the C_max and AUC will equal the one with a constant rate infusion.

❝ ❝ ❝

❝ ❝ ❝ […] if the dose is not lost, can i say just the AUC will be effect but the Cmax is the same with the canstant rate infusion?

❝ ❝

❝ ❝ Read again what I wrote above.

❝

❝ So, you mean the Cmax and the AUC both will equal the one with a constant rate infusion?

Yes!

❝ Don't we need to consider the eliminate rate?

Why? Elimination is independent from any kind of input.

❝ if we speed up the infusion rate while the eliminate rate is not change, the Cmax won't be greater than the constant rate infusion?

Again: yes.

In my simulations I assumed:

1. ▬▬ D=1 with a constant infusion rate of 2 h^–1 (i.e., infusion time of exactly 30 minutes).
   
2. ▬▬ D=0.5 with a constant infusion rate of 2 h^–1 (i.e., planned infusion time of exactly 30 minutes).
   Infusion completely stopped after 15 minutes for five minutes.
   Infusion of the remaining D=0.5 resumed at 20 minutes with an accelerated infusion rate of 3 h^–1 (i.e., infusion time of exactly ten minutes).

I have some doubts whether with your equipment (drip counter) you managed

1. to have the same infusion rate across all subjects (I guess in some infusion was completed earlier or later than at 30 minutes) and
   
2. to adjust an accelerated infusion rate properly.

ElMaestro had valid points as well. With an accelerated infusion rate you may run into safety problems.

Coming back to your very first question:

❝ Does the Cmax should be excluded? What about the AUC? What should the investigator to do if the same situation (need to stop temporarily or need to change the infusion speed) occurs next time?

For the next time I strongly recommend infusion pumps (yeah, I know, expensive): Exact infusion rates, no bubbles, no problems.
If you would have kept the original infusion rate (after the five minutes stop), i.e., complete it at 35 minutes, you would have seen a C_max which is 0.35% (!) lower than expected with the planned schedule – if you have an early sampling time point. If not, you will observed a lower C_max. How much lower depends on the sampling schedule and the elimination rate. Theoretically the AUC is not affected (depends only on the dose).

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PS: Why did it take the nurse five minutes to expel the bubble? In my experience about one minute should be sufficient. Would look like this: