Session 13
Pharmacology: Drug Interactions

• Poster 76: Effect of Simultaneous or Staggered Dosing of Saquinavir (SQV), Ritonavir (RTV), and Nelfinavir (NFV) on Pharmacokinetic (PK) Interactions (Authored by T. Blaschke, C. Flexner, L. Sheiner, and S. Rosenkranz. Stanford Univ., CA; Johns Hopkins Univ., Baltimore, MD; Univ. of California, San Francisco; and SDAC/Harvard School of Publ. Hlth., Boston, MA)
  Click here to view the original abstract

• Poster 77: Pharmacokinetic (PK) Drug-Interaction between Amprenavir (APV) and Ritonavir (RTV) in HIV-Seronegative Subjects after Multiple, Oral Dosing (Authored by B.M. Sadler, P.J. Piliero, S.L. Preston, L. Yu, and D.S. Stein. Glaxo Wellcome, Inc., Res. Triangle Park, NC; and Albany Med. Coll., NY)
  Click here to view the original abstract

• Poster 78: The Addition of a Second Protease Inhibitor Eliminates Amprenavir-Efavirenz Drug Interactions and Increases Plasma Amprenavir Concentrations (Authored by S. Piscitelli, C. Bechtel, B. Sadler, J. Falloon, and the Intramural AIDS Program. NIH, Bethesda, MD and Glaxo-Wellcome, Res. Triangle Park, NC)
  Click here to view the original abstract

There were quite a few posters reporting on interactions of antiretroviral drugs. Several of the more immediately relevant posters focused on using relatively low doses of ritonavir (Norvir) to lower the amount needed of other drugs, because ritonavir slows down the elimination of many drugs from the blood, by the liver. Amprenavir (Agenerase) is recommended in a dose of 1,200 mg twice a day -- which means eight pills twice a day, since each pill is only 150 mg. However, a dose of ritonavir of only 100 mg, when added to 600 mg of amprenavir, twice a day, gives the same, or even better, blood levels than the 1,200 mg dose (see: poster 77). A couple of notes of caution, though, is that this study was done in HIV-negative people and sometimes data from HIV-positive people may be different. Also, elevations in blood fats, cholesterol and triglycerides, were observed as a result of the addition of 100 mg of ritonavir. So one must ask if the added toxicity is worth it simply in order to take fewer pills a day.

Another poster, though, reported on the use of amprenavir with ritonavir, in a setting where it may be of greater help than just decreasing the number of pills you need to take (see: poster 78). When amprenavir is given with efavirenz (Sustiva), it significantly lowers the amount of efavirenz in the blood. When doses of 200 mg or 500 mg of ritonavir were added to amprenavir, 1,200mg, twice a day, and efavirenz, 600 mg, once a day, good levels of efavirenz in the blood were maintained. A similar benefit was seen with adding nelfinavir (Viracept), 1,250 mg, twice a day to amprenavir and efavirenz -- nelfinavir has fewer effects on raising blood fats.

Another poster studied the blood levels in people taking the common combination of ritonavir, and saquinavir, both at 400 mg twice a day (see: poster 76). This studied verified that the increases in saquinavir blood levels, due to ritonavir, is seen whether the pills are taken together, or a different times of day, separated by four hours.

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