| Autor: |
Raymundo Sanchez-Ponce, Li-Quan Wang, Wei Lu, Jana von Hehn, Maryann Cherubini, Roger Rush |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
|
| Zdroj: |
Metabolites, Vol 2, Iss 3, Pp 596-613 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
2218-1989 |
| DOI: |
10.3390/metabo2030596 |
| Popis: |
STX209 is an exploratory drug comprising the single, active R-enantiomer of baclofen which is in later stage clinical trials for the treatment of fragile x syndrome (FXS) and autism spectrum disorders (ASD). New clinical data in this article on the metabolism and pharmacokinetics of the R- and S-enantiomers of baclofen presents scientific evidence for stereoselective metabolism of only S-baclofen to an abundant oxidative deamination metabolite that is sterically resolved as the S-enantiomeric configuration. This metabolite undergoes some further metabolism by glucuronide conjugation. Consequences of this metabolic difference are a lower Cmax and lower early plasma exposure of S-baclofen compared to R-baclofen and marginally lower urinary excretion of S-baclofen after racemic baclofen administration. These differences introduce compound-related exposure variances in humans in which subjects dosed with racemic baclofen are exposed to a prominent metabolite of baclofen whilst subjects dosed with STX209 are not. For potential clinical use, our findings suggest that STX209 has the advantage of being a biologically defined and active enantiomer. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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