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?

Answer 1

The drugs can be administered to patients through one of several routes including routes of oral, topical or parenteral administration. Examples of parenteral routes of administration include intravenous, subcutaneous and intramuscular. Intravenous (IV) drug solutions can be given as a bolus dose (injected all at once) or infused slowly through a vein in the plasma at a constant rate or zero order. The main advantage of administering a drug by intravenous infusion is that the IV infusion allows precise control of the plasma concentrations of the drug to adapt to the individual needs of the patient. For drugs with a narrow therapeutic window (eg, Heparin), the intravenous infusion maintains a constant and effective plasma drug concentration by eliminating large fluctuations between the maximum (maximum) and minimum (minimum) concentration of drug in plasma. In addition, intravenous infusion of medications, such as antibiotics, can be given with intravenous fluids that include electrolytes and nutrients. In addition, the duration of drug therapy can be maintained or terminated as necessary by intravenous infusion.

he change in the amount of drug in the body at any time (dDB/dt) during the infusion is the rate of input minus the rate of output.

where DB is the amount of drug in the body, R is the infusion rate (zero order), and k is the elimination rate constant (first order).

Integration of and substitution of DB = CpVD gives:

As the drug is infused, the value for time