Pharmacokinetics

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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 (Cmax): 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 (Cmax) pretty quickly. The drug level then decreases as the drug is broken down and removed from the blood.
  • Minimum concentration (Cmin): This is the lowest level that a particular drug reaches in the blood. The lowest drug level, right before the next dose, is the (Cmin), 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 (t1/2): 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.

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 (Cmin) and total exposure (AUC) to be effective against HIV.

PK values are also used to help avoid toxic side effects. If the maximum concentration (Cmax) gets too high, the drug can cause many 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 the enzymes work slower. 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 (Cmin) 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. Several other PIs can be boosted with Norvir.

Health care providers should be aware of the pharmacokinetics of drugs and their interactions, and should 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.

Do Men and Women Process Drugs Differently?

There are some PK differences in men and women. At the same doses, some women have higher levels of certain drugs in their bloodstreams and experience more side effects than men. Despite the differences, women seem to benefit as much from HIV therapy as men.

These PK sex differences (male vs. female) may be related to hormone changes that occur when women get their periods. PK differences also may be linked to basic biology and physiology of cells (there are differences in the cells of men and women). They may also be linked to weight differences or differences in body composition (amount of fat vs. lean muscle).

Standard doses of drugs are usually based upon research done predominantly in men. This means a woman, who generally weighs less than a man, may get a higher amount of the drug in her body than is needed to be effective. Although differences between men and women have been seen in studies, no changes to dosing have been recommended for women. However, a few HIV drugs are given at lower doses if your weight is below a certain cut-off (e.g., Sustiva).

If you are experiencing side effects, ask your health care provider for help. Do not change your dose or stop your drugs without speaking to your provider.

Other factors can also affect PK, including:

  • Genetic differences in drug processing
  • Food
  • Tobacco and alcohol use
  • Drug interactions
  • Race/ethnicity
  • Hepatitis or other liver problems

Pharmacokinetic Testing

Because of PK differences, new tests are being developed to help figure out if patients are receiving the right amount of drug.

Therapeutic Drug Monitoring (TDM): TDM is designed to measure your drug levels specifically. Basically it measures minimum concentration (Cmin) by drawing blood before morning meds. This can help your health care provider decide if the dose of your HIV drugs should be changed. TDM is expensive and is most often used in research studies. It may or may not be available in your health care provider's office.

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.

How to Make PK Work for You

The timing of medication doses has been carefully calculated to keep the drug in your bloodstream at levels that will control HIV. When you do not take a dose on time, the blood level of the drug will fall too low to be effective.

When this happens, HIV has a chance to make more copies of itself, which causes your viral load to go up. Having too little of an HIV drug in your blood also makes it easier for HIV to become resistant to the drug you are taking, causing it to stop working. Consequently, your viral load could go up, your CD4 cells could go down, and you might need to change drug treatments. The best way to avoid this is to take your HIV drugs the way they are prescribed. This maintains the blood level of the drugs necessary to fight the virus effectively.

Additional Resources

Select the links below for additional material related to pharmacokinetics.

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