The liver does two things that can affect the levels of drugs in the blood supply.  First the liver can metabolize the drugs.  Second the liver can filter the blood removing the drug and excreating it in the bile.  Page 209 of the text discusses the BSP test for liver function.  This test only measures the ability of the liver to filter the drugs from the blood.  Hepatic clearence of a drug is a combination of metabolism and filtration.  Remember that only that portion of the drug in the blood unbound to protien can be filtered or metabolized.  Thus changes in protien binding affects all forms of excreation of the drug.

Total Clearance or Cl _tot  is made up of all the various pathways for clearance.  Renal clearance (Cl _ren)and Hepatic Clearance (Cl _hep) are the most common but as the book points out there are many other mior pathways for elimination of the drug from the body.

What happens to the drug if it is filtered by the liver into the bile?  It is then stored in the gall bladder and dumpted into the intestinal tract.  Once there it can be absorbed.  This process is called biliary recycling or enterohepatic reabsorption.  See the factors that affect this process on page 226 of your text.

If a drug is excreated unchanged in the urine we can use the amount of drug excreated in the urine in place of blood levels to measure the pharmacokinetic parameters.  Chapter 19 discusses how to use urinary data to estimate blood levels.

For a one compartment model the amount of drug excreated into the urine each time period (hour) is proportional to the amount of drug in the body during that time period.

The amount of drug in the body is the concentration in the blood supply times the volume of distribution
        A = C X Vd

The amount excreated in the urine is a function of the rate constant for elimination, the amount of drug in the body, and the fraction of the dose that is excreated by the kidneys.

            Au = A ·k ·f

The use of urinary excreation is limited.  Please read pages 228 & 229

We will discuss table 19-1 in class.  Please review it before class.

The Area Under the Curve (AUC) is directly proportional to the amount of drug that has reached the systemic circulation.  It is used to estimate the amount available by comparing the AUC for an IV dose to the AUC for a non-IV dose.  This one paramater is key to understanding the equivalence of generic drug products and the effectiveness of a particular dosage form.

Measuring or calculating the AUC is a easy but time consumming process.  The most common method is the trapazoidal rule. This method divides the curve into a series of trapazoids.  The area of each is claculated and then added together to get the total AUC between two times.  Please use the data in the previous pages to practice the claculation of the AUC from zero time to the last data point.  The area of a trapazoid is the average height times the width.  For our situation this means that we average the blood level values for each segment of the curve and multiply by the time between those two points.  (C₁ + C₂)/2 Times t₂ -t₁

The AUC from the last data point to infinity is estmated by assuming that at that stage in the blood level curve ONLY first order elimination is occuring.

With that assumption the AUC from the last data poit to infinity can be calculated by dividing the last data point by the rate constant for elimination

            C_last/ke

Please do this claculation on the test data and add it to the previous claculated AUC_{0 to t}