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Antimanic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Aman Upaganlawar, Abdulla Sherikar, Chandrashekhar Upasani
Oxcarbazepine shares the similar structural properties as that of carbamazepine and it is a prodrug. After administration, oxcarbazepine is immediately changed to its 10-hydroxy derivative, called as monohydroxy derivative (licarbazepine). Oxcarbazepine has similar mechanism of action property as that of carbamazepine, oxcarbazepine bind to the alpha subunit of VSSCs and causes the inhibition of VSSCs which is similar to carbamazepine. Being as less sedative and more tolerable, rate of incidence of bone marrow toxicity with oxcarbazepine is less as compared to carbamazepine, therefore oxcarbazepine is used as “off label” drug by many clinicians for the manic phase of bipolar disorder (Golan, 2012; Brunton et al., 2011; Katzung et al., 2009).
Hydrolytic Enzymes for the Synthesis of Pharmaceuticals
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Sergio González-Granda, Vicente Gotor-Fernández
Eslicarbazepine, also known as (S)-Licarbazepine (Scheme 9.24) is the pharmacologically active form of antiepileptic drugs such as carbamazepine (also known as Tegretol®) and oxcarbazepine (also known as Trileptal®). Its racemic mixture has been subjected to kinetic resolution using various lipases, finding CRL as the most selective one although with moderate values (El-Behairy and Sundby, 2016). From the four tested vinyl esters (acetate, propionate, butyrate and benzoate), the best conditions were found using 2 equiv. of vinyl benzoate and tert-butyl methyl ether (TBME) as solvent. The (R)-ester and the (S)-alcohol were isolated in 77 and 97% ee, respectively, after 5 days at 40°C, which are much better results than the ones obtained by complementary resolution of the corresponding racemic esters using a hydrolytic procedure (21–98% conversion and E = 1–5 after 48 h). KR of Licarbazepine using CRL and vinyl benzoate in TBME.
E
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Eslicarbazepine acetate is rapidly and extensively biotransformed to its major active metabolite eslicarbazepine by hydrolytic first-pass metabolism. Minor metabolites in plasma are R-licarbazepine and oxcarbazepine, which were shown to be active, and the glucuronic acid conjugates of eslicarbazepine acetate, eslicarbazepine, R-licarbazepine and oxcarbazepine.
Population pharmacokinetics of oxcarbazepine: a systematic review
Published in Expert Review of Clinical Pharmacology, 2021
Yue-Ting Chen, Chen-Yu Wang, Yi-Wei Yin, Zi-Ran Li, Wei-Wei Lin, Min Zhu, Zheng Jiao
Oxcarbazepine is completely absorbed (>95%) and quickly transformed to its active metabolite 10-hydroxycarbazepine (MHD), also called licarbazepine, by cytosolic enzymes in the liver after oral administration [5,6]. Owing to its rapid metabolism, the area under the concentration-time curve (AUC) of OXC is at least 90% lower than MHD in vivo [7]. Thus, the effectiveness of OXC is mainly determined by measuring MHD concentration [8]. Following OXC administration, the concentration of MHD reaches a peak in approximately 2–4 h [9]. MHD has a low protein binding rate (~39%) [10], and its volume of distribution (Vd) is between 0.3 and 0.8 L/kg [6]. MHD is excreted unchanged in the urine (27%) or eliminated in conjugation with uridine diphosphate-glucuronosyltransferase (UGT) (49%), with only a small fraction (4%) being oxidized to its dihydroxy derivative (DHD), while OXC and its conjugated metabolites (9%) are excreted in the urine [5,11].
Translational issues in precision medicine in neuropathic pain
Published in Canadian Journal of Pain, 2020
Anthony H. Dickenson, Ryan Patel
Based on this study, we recorded activity in thalamic neurons in a model of neuropathy and studied the effects of the drug and the effects of lidocaine, another sodium channel blocker.14 Because the clinical study had used systemic administration, we also aimed to localize the site of action of these ion channel blockers. We studied both ongoing and evoked responses of the neurons in the pathways behind sensory components of pain and spontaneous activity in the thalamus. A marked reduction in spontaneous activity was seen after spinal lidocaine, with no effect being seen in sham rats. This measure was partly driven by ongoing peripheral activity because intraplantar lidocaine also reduced this ongoing thalamic neuronal firing. Systemic oxcarbazepine in neuropathic animals markedly inhibited evoked responses, namely, punctate mechanical, dynamic brush- and cold-evoked neuronal responses in the thalamus and dorsal horn, but did not show a marked effect on heat-evoked firing yet inhibited spontaneous activity in the thalamus. Intraplantar injection of the active metabolite licarbazepine replicated the effects of systemic oxcarbazepine, supporting a peripheral locus of action.
Silymarin as a flavonoid-type P-glycoprotein inhibitor with impact on the pharmacokinetics of carbamazepine, oxcarbazepine and phenytoin in rats
Published in Drug and Chemical Toxicology, 2021
Ana Ferreira, Márcio Rodrigues, Sara Meirinho, Ana Fortuna, Amílcar Falcão, Gilberto Alves
In line with these findings, as a possible strategy to overcome the pharmacoresistance phenomenon in epilepsy, it is fully justified the in vivo evaluation of the effect of silymarin on the pharmacokinetics of commonly prescribed AEDs widely recognized as P-gp substrates. Therefore, the present work was designed to investigate whether the pre-administration of silymarin to rats is able to change the rate and extent of drug exposure to carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT), as well as to their main metabolites carbamazepine-10,11-epoxide (CBZ-E), licarbazepine (LIC), and 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) (Figure 2).