FDA grant to help scientists increase generic drugs delivered vaginally or to the uterus

BUFFALO, N.Y. ¬- University at Buffalo researchers received an $880,000 grant to help quicken the development of generic equivalents of contraceptives and other drugs delivered vaginally or to the uterus, such as by intrauterine devices (IUD).

The investigators will develop a model of the female reproductive tract based on physiological measurements and mathematics that will become a platform to test drugs delivered this way, a route more complex than administering medication through the mouth, vein, muscle or skin.

The research, supported by a two-year grant from the U.S. Food and Drug Administration (FDA), is led by Robert Bies, PharmD, PhD, associate professor in the UB School of Pharmacy and Pharmaceutical Sciences.

Additional investigators include Sharon Achilles, MD, PhD, assistant professor, and Lisa Rohan, PhD, professor, both at the Magee-Womens Research Institute and the University of Pittsburgh.

“This work represents an exciting opportunity to apply mathematical modeling and simulation techniques (pharmacometrics) in conjunction with experimental approaches to facilitate the understanding of drug delivery in the vaginal and uterine spaces,” says Bies.

Of the 21 drugs delivered intravaginally or by IUD — which includes contraceptives, antibiotics, antifungals and more — only four have a generic equivalent, leaving few cost-effective treatment alternatives for women.

These medications treat a range of conditions, from preventing unwanted pregnancy and controlling infections to fighting cervical cancer.

The lack of generic drugs is partially tied to the complexity of intravaginal and intrauterine delivery, says Bies. The challenges of measuring drug release and absorption rates in vaginal and uterine tissues make it difficult for scientists to determine if a generic drug is bioequivalent, or has the same effect, as its brand name counterpart.

Creating a physiological modeling and simulation platform will allow researchers to predict the behavior of drugs within female reproductive tissues, and could significantly shorten the time needed to test bioequivalency and quicken the development of inexpensive, generic medications.

“Given the dynamic and complex nature of the female reproductive tract, simulation models such as that being developed are critical to enhance efficiency of the development of safe and effective female drug products,” says Rohan. “This can potentially make new products available to women in a more rapid timeframe.”

The investigators will expand on a recently developed model that successfully predicted drug concentrations of a microbicide delivered vaginally. The model will be extended to simulate the physiology of the uterus, cervix and rectum.

The new model will utilize lab-generated data as well as clinical data collected from women enrolling in a clinical study at the UPMC Magee-Womens Hospital at the University of Pittsburgh.

The model will estimate drug permeation rates, release rates and absorption rates of levonorgestrel — a hormonal medication commonly used in birth control — in the various tissue areas, as well as across the body when delivered by an IUD.

Once the model can accurately predict levels of levonorgestrel concentration, the platform will be expanded to include other drugs.

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