August 31, 2000
Once absorbed by the body, most drugs are carried to the liver. The liver contains many enzymes that help the body process drugs. Some anti-HIV therapies, including protease inhibitors and non nucleoside analogues, influence the way a group of liver enzymes called CYP3A behave. As a result, levels of other medications that are processed by the same enzymes can be affected. In some cases, the interaction can cause an increase in the drug level and in others a decrease.
Researchers in Boston conducted several short experiments on six healthy, non-smoking HIV-negative males. They gave the subjects standard doses of the sleeping medications Halcion (triazolam) or Ambien (zolpidem) or placebo along with ritonavir (Norvir). The researchers found that ritonavir boosted Halcion levels to twice what they would be under normal conditions. As well, levels of Halcion remained higher than normal for more than a day after a single dose was taken with ritonavir. Levels of Ambien were increased only slightly, probably because Ambien is processed by enzymes other than CYP3A.
Some confirmation of the work done in Boston has come from Europe. In laboratory experiments using liver cells, researchers in Helsinki found that ritonavir clearly impaired the liver's processing of Halcion. As well, they found that another protease inhibitor, amprenavir (Agenerase), also had a similar impact.
These results confirm the warning issued by the manufacturer of ritonavir to the effect that these sleeping medications should not be used by people taking ritonavir.
Journal of Acquired Immune Deficiency Syndromes 2000;24:129-136.
From Canadian AIDS Treatment Information Exchange (CATIE). For more information visit CATIE's Information Network at www.catie.ca