SOUTH SAN FRANCISCO, Calif., June 18, 2013 (GLOBE NEWSWIRE) -- Hyperion Therapeutics, Inc. (Nasdaq:HPTX) today announced that population pharmacokinetic (PK) modeling and dosing simulations were reported in The Journal of Clinical Pharmacology based on data from four Phase 2 and 3 trials that collectively enrolled patients with urea cycle disorders (UCDs) ages 2 months to 72 years. The final model described the differences in absorption rate and pharmacokinetic profiles of the company's two drugs, RAVICTI® (glycerol phenylbutyrate) Oral Liquid and BUPHENYL® (sodium phenylbutyrate) Tablets and Powder, in patients with UCDs. The article is available through the Wiley online library ( http://onlinelibrary.wiley.com/doi/10.1002/jcph.92/abstract ).
UCDs represent a collection of inherited enzyme and transporter deficiencies that impair the synthesis of urea, the body's vehicle for waste nitrogen removal via the urine, which results in affected patients suffering from high systemic levels of ammonia, a potent neurotoxin. Since UCDs constitute an ultra-orphan population with an estimated U.S. patient pool of approximately 1000, population PK modeling and dosing simulations were performed to help define the clinical pharmacology of the two compounds as well as metabolite exposure in pediatric and adult UCD patients.
The final model helps explain differences in the level of plasma metabolites (drug breakdown products) during dosing of the two drugs based on differences in the amount of drug metabolized to phenylacetylglutamine prior to reaching the systemic circulation. Moreover, during dosing with RAVICTI as compared with BUPHENYL, phenylbutyric acid is absorbed 70-75% more slowly and blood metabolite levels generally show less fluctuation."These modeling data are particularly interesting in that the slower input of the active ingredient into the circulation with RAVICTI as compared with the bolus type drug release of BUPHENYL may allow for more sustained ammonia control," said Dr. George Diaz, Associate Professor, Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine.