Pharmacokinetics

Table of Contents

• What Is PK?
• How Is PK Studied?
• Drug Interactions and Drug Boosting
• Do Men and Women Process Drugs Differently?
• Pharmacokinetic Testing
• How to Make PK Work for You

What Is PK?

Pharmacokinetics, also known as PK, is the study of how medications behave in and move through the body. PK is used to figure out how much drug gets into your bloodstream and how long it stays there.

Scientists study PK to determine the best dose for an HIV drug. The dose must be high enough to keep HIV from reproducing, but not so high that it causes many side effects.

How Is PK Studied?

The following PK values are important:

• Maximum concentration (C_max): This is the highest level that a particular drug reaches in the blood. When a drug is given, it reaches its peak level in the blood (C_max) pretty quickly. The drug level then decreases as the drug is broken down and removed from the blood.
• Minimum concentration (C_min): This is the lowest level that a particular drug reaches in the blood. The lowest drug level, right before the next dose, is the (C_min), or "trough" level.
• Area Under the Curve (AUC): This refers to a graph showing the drug level in the blood over time and shows total drug exposure. The total exposure to the drug with each dose is called the AUC.
• Half-life (t_1/2): A drug's half-life is the amount of time required for half of the drug to be removed from the bloodstream. For example, if the dose of a drug is 100 milligrams (mg), and the half-life is eight hours, 50 mg will be left in the blood after eight hours.
• Inhibitory Quotient (IQ): The IQ of a drug shows how much drug is necessary to control the virus effectively. The IQ is different for each drug.

The PK values are used to figure out the correct dose -- both the amount of drug and the timing (once a day, twice a day, etc.). In order for a drug to work, it must have a high enough minimum concentration (C_min) and total exposure (AUC) to be effective against HIV.

PK values are also used to help avoid toxic side effects. If the maximum concentration (C_max) gets too high, the drug can cause unwanted side effects. The goal of HIV therapy is to get the most benefit from the drug with the fewest side effects.

Last but not least, the half-life of the drug must be long enough to allow for a reasonable dose schedule. Several drugs have a long enough half-life that they only need to be taken once a day.

Drug Interactions and Drug Boosting

Liver proteins called enzymes help with drug processing. Enzymes affect drugs by breaking them down. But enzymes are also affected by drugs.

This has proven to be very useful in HIV therapy. Here is an example: Norvir (ritonavir) is a protease inhibitor (PI) that makes some enzymes work more slowly. This keeps other drugs in the body longer. So if Norvir is given with another PI, like Reyataz (atazanavir), it "boosts" Reyataz by preventing it from being broken down as quickly by the liver. Boosting with Norvir increases both the minimum concentration (C_min) and total exposure (AUC) of Reyataz. As a result, Reyataz can be given once a day with a little Norvir. The boosted regimen makes Reyataz more effective. The majority of PIs are boosted with Norvir.

Health care providers who are aware of the pharmacokinetics of drugs and their interactions will make sure you get the right doses. That is why it is so important to let your provider know about all the medications and supplements you are taking (including herbs, prescriptions, over-the-counter, and street drugs). It is okay to ask your health care provider to check to see if any of your drugs interact with each other or anything else you take.