AI Article Synopsis
- Trofinetide is the first approved treatment for Rett syndrome, and the study examines how liver impairment affects its pharmacokinetics (PK).
- Researchers used modeling to analyze drug concentration in virtual patients with varying degrees of liver impairment compared to healthy individuals after taking a 12 g dose.
- The results showed that liver impairment doesn't significantly impact trofinetide exposure, though slight increases in drug concentration were observed with more severe liver conditions due to hematocrit changes.
Article Abstract
Introduction: Trofinetide is the first drug to be approved for the treatment of Rett syndrome. Hepatic impairment is not expected to affect the pharmacokinetic (PK) profile of trofinetide because of predominant renal excretion. This study was conducted to help understand the potential impact of any hepatic impairment on trofinetide PK.
Methods: This study used physiologically based PK modeling to estimate trofinetide exposure (maximum drug concentration and area under the concentration-time curve from time zero to infinity) in virtual patients with mild, moderate, and severe hepatic impairment (per Child-Pugh classification) compared with virtual healthy subjects following a 12 g oral trofinetide dose.
Results: In individual deterministic simulations for matched individuals and stochastic simulations at the population level (100 virtual individuals simulated per population), as anticipated, predicted plasma exposures were similar for healthy subjects and for patients with mild, moderate, and severe hepatic impairment. However, predicted blood concentration exposures slightly increased with increasing severity of hepatic impairment because of change in hematocrit levels.
Conclusion: This study indicates that hepatic impairment is not expected to have a clinically relevant effect on exposure to trofinetide.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263405 | PMC |
| http://dx.doi.org/10.1007/s12325-024-02926-6 | DOI Listing |
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