Impact of Severe Sepsis or Septic Shock on Drug Response

Vázquez, Marta; Fagiolino, Pietro; Maldonado, Cecilia; Ibarra, Manuel; Boronat, Anna

doi:10.5772/27349

Cited by 1 publication

(1 citation statement)

References 34 publications

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“…Too little drug exposure leads to ineffective regimens, whereas too much creates the risk of adverse effects. Pathology itself can be the cause of pharmacokinetic variability [ 4 – 6 ]. Finally, although drug concentrations at the different sites are always responsible for the therapeutic or toxic effects observed, we have to be aware of the concentrations we are referring to: parent drug, metabolite, and free plasma drug concentration.…”

Section: Introductionmentioning

confidence: 99%

Hyperammonemia Associated with Valproic Acid Concentrations

Vázquez

Fagiolino

Maldonado

et al. 2014

BioMed Research International

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Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%). Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily) formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.

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Section: Introductionmentioning

confidence: 99%