Study: Many HIV-infected African Americans can receive effective doses of maraviroc medicines -
Many African Americans may not receive effective doses of the drug maraviroc HIV, a new Johns Hopkins study suggests. Initial dosing studies, completed before the drug was approved in 07, included most European Americans, who generally lack a protein that is key to remove the body maraviroc. The current study shows that people with the maximum levels of the protein - almost half of African Americans - are left with less maraviroc in their bodies compared with those lacking protein, even when given the same dose. A simple genetic test for the gene that makes the protein CYP3A5 could be used to determine the doses would achieve effective levels in individuals, the researchers say.
The results of the small study were published online Aug. 12 in the journal Drug Metabolism and Disposition .
"Because African Americans are disproportionately affected by HIV infection, it is doubly important that we have the right dosage," said Namandje Bumpus, Ph.D., Assistant professor of pharmacology and molecular sciences at the medical school at Johns Hopkins University.
CYP3A5 is a protein that is abundant in the liver and intestinal cells. it adds an oxygen molecule various drugs to make them more soluble in water, so they can get in the end of the urine and leave the body. Eighty to 0 percent of European Americans not CYP3A5, because they have inherited two copies of the CYP3A5 gene dysfunctional
Normally, the absence of CYP3A5 is not noticeable. a very similar protein, CYP3A4, acts on most of the same drugs. However, for some drugs as maraviroc and drug vincristine against cancer, CYP3A5 appears to play a particularly important role in helping to remove the body. In these cases, the presence or absence of CYP3A5 would probably affect the amount of drug in the blood, the Johns Hopkins team predicted. And since 85 percent of participants in the study of maraviroc dosage were European Americans, who generally lack functional CYP3A5, researchers have hypothesized that the recommended dose for maraviroc could be too low for those two functional copies of the gene - which 45 percent of Africa -Americans
to test this idea, the research team gathered 24 healthy volunteers according to the number of functional copies of the CYP3A5 gene they had -. zero, one or two. They each received a single dose of maraviroc in the recommended dose of 300 milligrams, and the blood of each participant was taken at 10 time points over 32 hours.
In almost all time points, maraviroc concentrations were similar for the groups with zero or one functioning copies of CYP3A5, but were lower in those with two copies of operation. Compared to those two malfunctioning gene copies, those with two copies running had a concentration of 41 percent lower overall. It is important, as a group, those with two functional copies had an average concentration which was just above the lowest level determined to be effective against the virus. And four of eight had average concentrations of individual who dropped below.
"The trend that we saw was that the most functional CYP3A5 a person had, the faster maraviroc was treated and left the body, the higher its concentration in the blood," says Bumpus. "What is is that if a larger study confirms that we are under-dosing of this group, a simple genetic test before dosing decisions could remedy the situation. "
She adds that this study shows highlight the importance of clinical trial design in which participants are as ethnically diverse as the population to be treated.
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