Pharmacokinetic (PK) boosting is a strategy of antiretroviral therapy that is becoming more widely used clinically. It is also being employed in clinical trials to further evaluate its safety and efficacy. PK boosting and the principles behind the concept can be complex, and they need to be demystified and be part of any meaningful clinical discussion. The pharmacokinetics of a drug are the processes by which it is absorbed, metabolized, distributed, and excreted by the body. During drug trials, dosing is optimized to reach and maintain a certain level in the body that is considered therapeutic without causing toxicity. When any of these pharmacokinetic pathways are altered, the amount of drug that is available for use by the body is either increased or decreased. The pathways can be altered due to decreased function of the liver or kidneys, food intake with medications, or interactions with other medications--both prescribed and over-the-counter.

When medications are metabolized by the liver, enzymes such as cytochrome P450 (CYP450) are involved in the process. Some medications have a major effect on this enzyme and the metabolism of concurrent medications. The overall effect of this process is that the therapeutic level of a drug can be increased or decreased or be unaffected depending on which other medications are given with it. When certain medications are given together, doses may need to be adjusted to maintain therapeutic levels of all the drugs involved or to prevent toxicities.  Because many of the medications used in HIV disease management as well as in the treatment of opportunistic infections are metabolized using the CYP450 enzyme system, they may interact with one another. Researchers have speculated that this synergistic effect could be used to the patient's advantage and might provide a realistic way to clinically reduce pill burden, increase adherence, and improve quality of life.

PK boosting, the ability of one drug to increase levels of another drug, is being actively pursued, especially with regard to antiretroviral medications. When an antiretroviral medication, primarily a protease inhibitor, is boosted, both the dosage and the frequency of the dose may be need to be decreased.

Ritonavir (Norvir¨) is the antiretroviral most commonly used to boost other protease inhibitors because it is a potent inducer of the CYP450 enzyme. Ritonavir is given in very small doses (100 mg or 200 mg) in combination with other protease inhibitors to change the frequency of protease inhibitors from three times a day to twice a day; indinavir (Crixivan¨) is combined with ritonavir, for example, to produce this result. Once-daily dosing can often be accomplished by combining saquinavir (soft-gel Fortovase¨, for example) with certain protease inhibitors.

Lopinavir formulated with ritonavir (Kaletra¨) is the first antiretroviral that combines two protease inhibitors in the same capsule. Lopinavir is boosted to therapeutic levels by a low dose of the ritonavir.

PK boosting may not necessarily decrease the pill burden of antiretroviral regimens; however, it has made the regimens easier to take by decreasing the frequency of the doses. Many of these and other dosages are currently being studied further in clinical trials to assure that the therapeutic benefit is the same or better without causing toxicities. PK boosting is also being researched to determine what medications can benefit from this process as well as which medications can be given in combination to achieve a therapeutic outcome. It is also very important to remember that the drug interactions used in PK boosting can occur with any number of prescription and over-the-counter medications and herbal supplements as well. Any questions that may arise should be directed to your healthcare provider or pharmacist.

Christine A. Balt, MS, RN, ACRN, APRN, BC is a Family Nurse Practitioner in the Infectious Disease Clinic at Wishard Health Services, Indianapolis, IN and the Indiana University Department of Medicine, Division of Infectious Diseases.

References

The following materials were consulted in the preparation of this article:

Hoetelmass R. The concept of protease inhibitor boosting. Basel, Switzerland: FSP International; 2000.

     Flexner C, Piscitelli S. The clinical management

of HIV/AIDS: drug-drug interactions. 1999. Available at: <http://www.medscape.com/medscape/ HIV/ClinicalMgmt/CM.drug/pnt-CM.drug.html>.