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→Structure and interaction with albumin
==Structure and interaction with albumin==
VPA (2‐propyl‐pentanoic acid) is a short-chain fatty acid ingested administered intravenously or orally as sodium valproate, composed of sodium and VPA in a 1:1 molar ratio. VPA itself is highly hydrophobic, leading to a favourable entry to the central nervous system with good oral bioavailability. <ref name=”[1]”> Williams, J. H., Jayaraman, B., Swoboda, K. J., & Barrett, J. S. (2011, December 13). Population Pharmacokinetics of Valproic Acid in Pediatric Patients With Epilepsy: Considerations for Dosing Spinal Muscular Atrophy Patients. Retrieved October 17, 2019 , at [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345311/ “https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345311/”].</ref>
VPA in the blood exists in its free form as the valproate ion, but is highly bound to serum proteins. It mainly binds to albumin (90 - 95%), <ref name=”[2]”> Dasgupta, A. (2016). Chapter 4 - Monitoring Free Drug Concentration: Clinical Usefulness and Analytical Challenges. Retrieved October 17, 2019 , at [https://doi.org/10.1016/B978-0-12-802025-8.00004-0 “https://doi.org/10.1016/B978-0-12-802025-8.00004-0”].</ref>
with the unbound fraction increasing linearly from approximately 10% at 50 mg/L to approximately 30% at 200 mg/L total concentrations. <ref name=”[1]”> Williams, J. H., Jayaraman, B., Swoboda, K. J., & Barrett, J. S. (2011, December 13). Population Pharmacokinetics of Valproic Acid in Pediatric Patients With Epilepsy: Considerations for Dosing Spinal Muscular Atrophy Patients. Retrieved October 17, 2019 , at [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345311/ “https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345311/”].</ref>
Phenytoin, another well-known anti-epileptic drug (AED), is a competitor in this protein binding. This means that VPA binding to albumin decreases if phenytoin is taken, causing both free drug concentrations to increase. <ref name=”[3]”> Cramer, J. A., & Mattson, R. H. (1979). Valproic acid: in vitro plasma protein binding and interaction with phenytoin. Retrieved November 6, 2019 , at [https://www.ncbi.nlm.nih.gov/pubmed/121944 “https://www.ncbi.nlm.nih.gov/pubmed/121944”].</ref>
== Mechanism of action ==
===Pathophysiology of epilepsy===
