Eslicarbazepine acetate

A: Eslicarbazepine acetate itself is a prodrug, meaning it is inactive until metabolized in the body. Its major active metabolite, Eslicarbazepine, exerts its antiepileptic effects primarily by stabilizing the inactivated state of voltage-gated sodium channels (VGSCs) []. This prevents the channels from returning to their active state, thereby inhibiting the repetitive firing of neurons that underlies epileptic seizures.

A: Yes, research suggests that ESL exhibits maintained use-dependent blocking effects in both human and experimental epilepsy models. Furthermore, it demonstrates significant add-on effects when used with Carbamazepine in human epilepsy [].

A: Studies have shown that ESL also inhibits Cav3.2 T-type Ca2+ channels. These channels are thought to play a crucial role in the process of epileptogenesis, which is the development of epilepsy [].

ANone: this compound has the molecular formula C18H18N2O3 and a molecular weight of 310.34 g/mol.

A: Yes, various spectroscopic techniques, including Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), and differential scanning calorimetry (DSC) have been used to characterize ESL and its formulations [, , ]. These techniques provide information about the drug's structural properties, crystallinity, and thermal behavior.

ANone: this compound is not known to possess catalytic properties and is not used for catalytic applications. Its primary function is as a pharmaceutical drug.

A: Yes, computational studies, including molecular docking simulations, have been employed to investigate the interactions of ESL with its molecular targets, such as VGSCs and BACE1 []. These studies can provide insights into the binding affinities and molecular mechanisms of action.

A: ESL shares structural similarities with other dibenzazepine antiepileptic drugs like Carbamazepine and Oxcarbazepine. The S (+) enantiomer of licarbazepine, the active metabolite of ESL, is thought to be responsible for its enhanced efficacy and reduced side effects compared to the racemic mixture found in Oxcarbazepine []. The absence of the 10,11-epoxide group in ESL, unlike Carbamazepine, contributes to its lower drug interaction potential and improved neurological tolerability [].

A: Researchers have investigated various formulation strategies for ESL, including tablet formulations [, ], oral suspensions [, ], and formulations suitable for delivery via enteral feeding tubes []. These formulations aim to optimize drug solubility, dissolution rate, and bioavailability.

A: Studies indicate that ESL oral suspensions prepared with specific vehicles, such as a 50:50 v/v mixture of Ora-Sweet or Ora-Sweet SF with Ora-Plus, demonstrate good stability for up to two months when stored at room temperature or under refrigeration [, ].

ANone: Information about specific SHE regulations related to ESL research and manufacturing is not directly addressed in the provided research papers.

A: ESL is rapidly and extensively metabolized in the liver, primarily by esterases, into its major active metabolite, Eslicarbazepine (S-licarbazepine) [, , , ]. Minor metabolic pathways include oxidation to Oxcarbazepine and formation of R-licarbazepine [].

A: Studies indicate that food does not significantly impact the pharmacokinetics of ESL, making it convenient for once-daily dosing [, , ].

A: Research has identified that the enzyme AADAC plays a significant role in the hydrolysis of ESL to its active metabolite Eslicarbazepine in the human liver and intestines []. Notably, genetic variations (polymorphisms) in the AADAC gene can influence enzyme activity and potentially impact drug response [].

A: Yes, numerous clinical trials have demonstrated the efficacy of ESL as adjunctive therapy in adults with refractory focal-onset seizures. Significant reductions in seizure frequency and improved responder rates were observed compared to placebo, particularly at doses of 800mg and 1200mg once daily [, , , , , ].

A: Clinical trials have shown promising results for ESL monotherapy in adults with newly diagnosed focal-onset seizures, demonstrating good tolerability and effectiveness over the long term [, ]. Additionally, patients transitioning from controlled-release Carbamazepine monotherapy to ESL monotherapy showed comparable efficacy and safety profiles [].

A: Preliminary research suggests that ESL might hold promise in treating other neurological disorders, such as neuropathic pain, including diabetic neuropathic pain and postherpetic neuralgia. This is based on its similarities in structure and mechanism of action to Carbamazepine and Oxcarbazepine, which are known to be effective in these conditions [].

ANone: The provided research papers do not extensively discuss specific resistance mechanisms to ESL or cross-resistance with other antiepileptic drugs.

ANone: Information regarding the toxicology and safety profile of ESL is not included in this scientific Q&A, as the focus is on the scientific aspects of the compound.

ANone: The provided research papers primarily focus on conventional oral administration of ESL. Targeted drug delivery approaches are not discussed within the scope of these studies.

ANone: The provided research papers do not mention any specific biomarkers associated with ESL treatment response or adverse effects.

A: High-performance liquid chromatography (HPLC) coupled with ultraviolet detection (HPLC-UV) is commonly used for the quantification of ESL and its metabolites in biological samples, particularly plasma [, , , ].

A: Yes, enantioselective HPLC methods utilizing chiral stationary phases, such as beta-cyclodextrin columns, are employed to separate and quantify the individual enantiomers of ESL's metabolites, particularly S-licarbazepine and R-licarbazepine [].

ANone: The provided research papers do not delve into the environmental impact or degradation pathways of ESL.

A: ESL is known to have poor aqueous solubility, which can limit its dissolution rate and, consequently, its oral bioavailability []. Therefore, various formulation strategies, such as particle size reduction and the use of solubility enhancers, have been explored to improve its dissolution characteristics and enhance its therapeutic effectiveness [].

A: Yes, studies have investigated techniques like co-grinding ESL with other compounds such as tartaric acid or citric acid to form eutectic systems []. These eutectic mixtures exhibit lower melting points and enhanced dissolution rates compared to the pure drug, leading to improved bioavailability [].

A: Several research articles highlight the development and validation of analytical methods, particularly HPLC-UV methods, for the quantification of ESL and its metabolites in various matrices, including bulk drug substance, pharmaceutical formulations, and biological samples [, , , ]. The validation processes typically involve assessing parameters such as linearity, accuracy, precision, specificity, sensitivity, and robustness to ensure the reliability and reproducibility of the analytical data [, , , ].

ANone: The specifics of quality control and assurance measures implemented during the development, manufacturing, and distribution of ESL are not elaborated upon in the provided research papers.

ANone: The provided research papers do not delve into the immunogenicity or potential for immunological responses associated with ESL.

ANone: Specific details regarding ESL's interactions with drug transporters are not discussed in the provided research papers.

A: ESL exhibits a low potential for inducing or inhibiting major drug-metabolizing enzymes, particularly cytochrome P450 enzymes [, , ]. This characteristic contributes to its favorable drug interaction profile, making it a suitable option for patients on multiple medications [, , ].

ANone: The provided research papers do not provide specific details regarding the biocompatibility or biodegradability of ESL.

A: ESL is often compared to other antiepileptic drugs, such as Carbamazepine, Oxcarbazepine, lacosamide, levetiracetam, and pregabalin, in terms of efficacy, tolerability, and safety [, , , , , ]. The choice of one drug over another is influenced by factors such as the patient's individual characteristics, seizure type, potential for drug interactions, and tolerability profile [, , , , , ].

ANone: The provided research papers do not address the aspects of recycling or waste management specific to ESL.

ANone: The research papers do not explicitly discuss specific research infrastructure or resources used in ESL studies.

A: ESL, under the brand name Zebinix®, received approval from the European Medicines Agency (EMA) in 2009 for use as adjunctive therapy in adults with partial-onset seizures [, ]. Subsequently, it gained approval from the US Food and Drug Administration (FDA) in 2013 under the brand name Aptiom™ for the same indication [].