Do drugs have different effects on males versus females?

Researchers examine drug-metabolizing enzyme, absorption of furosemide

The+UGT2B17+enzyme+is+three+to+five+more+times+fully+expressed+in+males+than+females.

GRACIE ROGERS

The UGT2B17 enzyme is three to five more times fully expressed in males than females.

GREY KAMASZ, Evergreen reporter

Bhagwat Prasad’s lab at WSU Spokane is examining drug effects in on males and females to find a correlation between an individual’s characteristics and the way their bodies process drugs.

Prasad, the Department of Pharmaceutical Sciences associate professor, runs the lab, which is funded by the National Institutes of Health, he said.

The goal of the laboratory is to understand the interindividual differences in drug effects, how drug effects differ for each individual, he said. The lab is interested in different factors like sex and genotype and how these factors affect drugs in the body.

“If we use the same [research methods for both sexes], there is a possibility the females can experience more toxicity for drugs because they are not tested in females,” Prasad said. “The clinical significance will be the safety of drugs in females [and] ultimately, we want to make sure we give [and] provide a safer dose of drugs to females.”

Prasad said he is investigating a protein called UGT2B17, a drug-metabolizing enzyme present in the liver and intestine. The protein is more present in males than females, because of its involvement in testosterone metabolism. The drug metabolism rate is higher in males than females due to the difference in testosterone.

Most drug clinical trials are done on male patients or subjects, like rats, he said. In the past, data gathered from clinical trials assumed females and males process drugs the same way. However, evidence has suggested females experience more drug side effects and higher rates of toxicity than males.

“If we use the same practice, there is a possibility the females can experience more toxicity for drugs because they are not tested in females,” Prasad said. “The clinical significance will be the safety of drugs in females. Ultimately, we want to make sure we give [and] provide a safer dose of drugs to females.”

Deepak Ahire, pharmaceutical sciences and molecular medicine graduate student, is also studying UGT2B17 and its expression in males and females in a separate project, he said.

“Deepak, my student, investigated around 100 drugs, and found around 25% of drugs he studied, which are marketed, [were] metabolized by UGT2B17, which was never studied in females versus males,” Prasad said. “We think these drugs could have some side effects that are specific in females but not in males.”

Ahire’s goal is to determine whether selected drugs are metabolized by the UGT2B17 enzyme, he said.

“[It is] one of the highly variable metabolizing enzymes, which exhibits dramatic and unusual interindividual variability in its expression and activity,” Ahire said.

The enzyme is three to five times more fully expressed in males than females due to the higher levels of testosterone, he said.

Another student in Prasad’s lab is Sheena Sharma, pharmaceutical sciences doctoral student and research lab assistant, who is researching the impact of an individual’s sex on furosemide, a diuretic drug given to patients with heart conditions. The drug is given to patients who need more water exertion from the body. Her goal is to see how the absorption of the drug differs in males versus females, she said.

She said it is important to study drug dosage adjustments for females to prevent toxicity concerns. Having an adequate dosage ratio can prevent these concerns in female patients.

The lab is using in-lab experiments and rat models as the research methods for their projects, she said. Male and female rats will be tested instead of just the former.

“We have conducted these studies in rats, but this research can be translated to humans as well,” Sharma said. “We found the levels of furosemide is higher in female rats as compared to the male rats, and it is actually two-fold higher in females as compared to males.”

For data analysis, the lab is using mass spectrometry techniques, where researchers take a small sample of the drug from the model’s blood and quantify the sample. The technique is used to measure the drug in the entire system through a small sample, Sharma said.

Prasad said the projects in his lab are in the beginning stage and have no set end date. They hope to make more progress and publish their research in the future.