An experiment is to be performed to test for the response of a drug in the liver

Question

An experiment is to be performed to test for the response of a drug in the liver.

This experiment will be performed on a rat and we know that we want the concentration in

the tissue of the liver to reach at least 5 mM. The average vascular volume in the liver of a

250 g rat is 0.556 mL while the total liver volume is 13.90 mL. In this experiment we are able

to infuse the drug such that the concentration in the blood rapidly reaches 200 mM and is

held constant at that level. The known permeability surface area product, PS, of this drug in

the liver is 0.025 mL/s. Estimate how long we should infuse the drug to reach a tissue

concentration of 5 mM? Are we able to also measure the response of a 10mM

concentration in the liver with this same protocol?

Explanation / Answer

ANSWER: A drug is administered to a rat of body weight 250g to perform an experiment of drug effect on the liver and 200 mM concentration of drug infused to reach the suitable concentration of that drug (5mM) in the tissue of liver.

If permeability surface area product (PS) of the drug to tissue is 0.025ml/s. Since, 200mM of drug present in 1liter therefore 5 mM of the same drug would be available in 25 ml of solution that is 40 times more than this.

Hence, we should infuse an average 200mM concentration of drug till 26.6 min (40/0.025 = 1600s) to reach an appropriate amount drug at 5mM to the tissue of liver. We can also find the response of 10mM of the same drug but for this we would have to infuse the drug to half the time period (13.3 min) of that takes to 5mM.

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