171 Ashley Ave.
Charleston, SC 29425
843-792-1414
800-424-MUSC
|
 |
July 2007
Children's Research Institute News Brief
 |
Bernard L. Maria, MD, MBA
Executive Director
Darby Children's
Research Inst. |
|
 |
Inderjit Singh, PhD
Scientific Director
Darby Children's
Research Inst. |
|
Transporters could more effectively deliver drugs to needed site
Researchers in the Charles P. Darby Children's Research Institute (DCRI) Laboratory of Drug Disposition and Pharmacogenetics think they may be able to improve the effectiveness of drugs by altering how they move through the body.
Drs. Lindsay DeVane, John Markowitz, and Jennifer Donovan are looking at the properties of proteins in the body known as "drug transporters." Drug transporters help move a drug through different barriers until it ends up where it's most needed.
"Drug transporters are sort of drug 'gatekeepers,'" says Dr. DeVane. "They are in a new category of proteins intensely researched in the last 10 years."
For example, to treat an illness that originates in the brain, a drug given by mouth must pass several barriers before reaching the site of action. "Drug transporters help move the drug through the body, through these barriers until it reaches its final destination," says Dr. DeVane.
The transporters assist the drug in passing through membranes in the gastrointestinal tract, where absorption into the blood takes place. These special proteins also help prevent the drug from being chewed up and eliminated by any of a multiple of enzymes in the liver, and then aid it in passing through tight junctions between cells located in what is called the blood-brain-barrier.
"For a drug that has poor brain penetration, a very high dose may enable it to reach the site of action in an amount sufficient to produce therapeutic benefits," explains Dr. DeVane. "However, the proper dose to get it to its ultimate site may be toxic to other organs in the body."
Since injecting a drug directly into the brain is not feasible, Drs. DeVane, Markowitz, and Donovan believe that manipulating the activity of drug transporters may allow useable amounts of a drug to reach critical sites.
"We're working at altering these transporters to improve drug delivery to the brain, which could prevent having to use intolerable amounts of the drug," explains Dr. DeVane.
With funding from the National Institute of Mental Health and the National Institute of Drug Abuse, the three researchers are looking at how antidepressants and psycho-stimulants interact with a drug transporter called P-glycoprotein.
By inhibiting the action of P-glycoprotein and related transporters in the blood brain barrier, more needed drug can pass through to produce beneficial effects. "We hope this could result in using lower doses of drugs if more of the drug is able to reach the site where it's needed."
These classes of drugs will hopefully serve as models for various other categories of drugs used to treat diseases in children and adolescents, explains Dr. DeVane. Currently, the DCRI group is working with Dr. Bernie Maria to investigate better methods to treat brain cancer in children through improved drug delivery.
"Generally, our knowledge about how the body handles and disposes of drugs usually comes from studies conducted in children long after investigations in various adult populations have been completed," says Dr. DeVane.
"This is one of the advantages of the DCRI - it allows us to apply scientific inquiry to children and adolescents early in the process of discovery."
|
|
Print Version