Researchers Finding May Boost Effectiveness Of Anti...( sent in the intestines where it preven...),Health

"Because HIV attacks the CD4-expressing lymphocytes circulating in the bloodstream, the goal of therapy would be to have an optimal level of the drug in the bloodstream so that the drug would get into to the CD4 lymphocytes and kill the virus," Kim said. "Pgp may prevent enough of the drug from getting into the bloodstream, and that may explain some of the drug failures."

Pgp is also expressed in the blood vessels lining the brain, known as the blood/brain barrier. Because HIV is known to take up residence in the brain, the researchers were interested in whether Pgp prevents protease inhibitors from crossing that barrier.

They found that when they injected protease inhibitors into mice that had been genetically engineered not to express Pgp, brain levels of the drugs climbed to seven-to-40 times higher than in mice that normally express PGP.

The researchers also found that brain levels of the protease inhibitors in normal mice were about one-tenth the blood level.

"The standard way to measure drug levels is in the blood, with the idea that if the blood level is adequate to kill the virus, we've given enough of the drug," he said. "Now the concern is that the brain level may be much lower and that the virus could escape to the brain, continue to divide there and live on."

Kim said he would next like to measure the levels of protease inhibitors in the cerebral spinal fluid of patients to determine -- at least indirectly -- whether a similar relationship exists in humans.

Another potential hide-out created by Pgp may be in some of the
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Contact: Matt Scanlan
matt.scanlan@mcmail.vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
15-Jan-1998