Dose Of Carbamazepine Research Articles

Frontline Sodium Channel-Blocking Antiseizure Medicine Use Promotes Future Onset of Drug-Resistant Chronic Seizures

The mechanisms of treatment-resistant epilepsy remain unclear. We have previously shown that frontline administration of therapeutic doses of lamotrigine (LTG), which preferentially inhibits the fast-inactivation state of sodium channels, during corneal kindling of mice promotes cross-resistance to several other antiseizure medicines (ASMs). However, whether this phenomenon extends to monotherapy with ASMs that stabilize the slow inactivation state of sodium channels is unknown. Therefore, this study assessed whether lacosamide (LCM) monotherapy during corneal kindling would promote future development of drug-resistant focal seizures in mice. Male CF-1 mice (n = 40/group; 18-25 g) were administered an anticonvulsant dose of LCM (4.5 mg/kg, i.p.), LTG (8.5 mg/kg, i.p.), or vehicle (0.5% methylcellulose) twice daily for two weeks during kindling. A subset of mice (n = 10/group) were euthanized one day after kindling for immunohistochemical assessment of astrogliosis, neurogenesis, and neuropathology. The dose-related antiseizure efficacy of distinct ASMs, including LTG, LCM, carbamazepine, levetiracetam, gabapentin, perampanel, valproic acid, phenobarbital, and topiramate, was then assessed in the remaining kindled mice. Neither LCM nor LTG administration prevented kindling: 29/39 vehicle-exposed mice were kindled; 33/40 LTG-exposed mice were kindled; and 31/40 LCM-exposed mice were kindled. Mice administered LCM or LTG during kindling became resistant to escalating doses of LCM, LTG, and carbamazepine. Perampanel, valproic acid, and phenobarbital were less potent in LTG- and LCM-kindled mice, whereas levetiracetam and gabapentin retained equivalent potency across groups. Notable differences in reactive gliosis and neurogenesis were also appreciated. This study indicates that early, repeated administration of sodium channel-blocking ASMs, regardless of inactivation state preference, promotes pharmacoresistant chronic seizures. Inappropriate ASM monotherapy in newly diagnosed epilepsy may thus be one driver of future drug resistance, with resistance being highly ASM class specific.

Effectiveness and Safety of Radiofrequency Thermocoagulation Treatment Guided by Computed Tomography for Infraorbital Neuralgia Following Failed Conservative Treatment: A Retrospective Study.

To evaluate the effectiveness and safety of CT-guided radiofrequency thermocoagulation (RFT) for the treatment of infraorbital neuralgia following the failure of conservative management. This was a single center, retrospective study which included 196 patients between the ages of 37 to 90 years, who suffered from infraorbital neuralgia, and had undergone CT-guided RFT treatment. The medical records of these patients were retrieved between January 7, 2015 and February 5, 2020, and the patients were followed up for 2 years. Follow-up outcomes included Numerical Rating Scale (NRS) scores, dosage of carbamazepine, time to take effect, status of recurrence and side effects. The effective rate was defined as the percentage of patients with postoperative NRS score reduction of >50%. The effective rates were 92.9%, 100%, 100%, 100%, 93.4% and 85.7% onthesame day, week 1, month 1, month 6, year 1 and year 2 after RFT, respectively. After RFT, the postoperative NRS scores and dosage of carbamazepine were significantly reduced than those preoperatively (P < 0.05). The median time to take effect was zero day. Twenty-eight patients with recurrence underwent RFT again and achieved complete pain relief. All patients experienced numbness in the infraorbital nerve innervation area and the numbness scores gradually decreased over time. CT-guided RFT treatment may be an effective and safe technique for pain relief in patients with infraorbital neuralgia following failed results from conservative treatment.

Influence of EPHX1 c.337T>C and UGT2B7*2 genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study.

Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having arole in the requirement of CBZ maintenance dose. The aim was to study the influence of EPHX1 c.337T>C and UGT2B7*2 genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy. Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10%EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of EPHX1 c.337T>C and UGT2B7*2, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between thegenotypes and CBZ maintenance dose requirement fordominant and recessive models of EPHX1 c.337T>C andUGT2B7*2. A value of p<0.05 was considered to be statistically significant. For UGT2B7*2 (rs 7439366), CT required a higher dose (CT 626mg/day and TT 523mg/day) but not found tobesignificant (p-value 0.167). PWE carrying CT genotypeofEPHX1 c.337T>C had 62mg higher dose when compared to homozygous mutant CC (590mg/day for CT and 528mg/day for CC) but p-value was not found to be significant (p-value 0.835). The results of our study done in 115 PWE showed there was a lack of association between SNPs of EPHX1 c.337T>C, UGT2B7*2 and CBZ maintenance dose requirement in Southern part of India and this finding has tobe confirmed in a larger sample size.

カルバマゼピン中毒により下眼瞼向き眼振を認めた薬剤性めまい症例

We report the case of a 33-year-old man who presented with disequilibrium and downbeat nystagmus. Balance testing showed failure of visual suppression of caloric nystagmus with insufficient optokinetic nystagmus responses, suggesting central vestibular dysfunction. However, MRI showed no lesions in the brain, including in the cerebellum. The patient had been diagnosed previously as having epilepsy, and the convulsions had remained under control for more than 10 years with a maintenance dose of carbamazepine (900mg/day). Blood tests revealed a serum level of carbamazepine of 10.7mEq/l, which was over the therapeutic range (4.0-10.0mEq/l). Therefore, his carbamazepine dose was reduced, and with a reduction of the dose to 600mg/day, his disequilibrium and downbeat nystagmus gradually disappeared, along with a decrease in return of the serum level of carbamazepine to the therapeutic range. Therefore, we diagnosed the disequilibrium with downbeat nystagmus in this patient as having been caused by carbamazepine intoxication. Although carbamazepine is metabolized by CYP3A4 in the liver, elevated levels of the drug have been reported in cases of renal failure. As he also suffered from polycystic kidneys, we consider that the progressive renal dysfunction in our patient could have precipitated the carbamazepine intoxication.

Characterizing complex and competing drug-drug interactions between the antiviral regimen of glecaprevir and pibrentasvir with rifampin or carbamazepine.

The fixed-dose combination of the direct acting antivirals glecaprevir (GLE) and pibrentasvir (PIB) is an oral, once-daily treatment for all six major genotypes of chronic hepatitis C virus infection. A single and multiple-dose rifampin study (N=12) and a carbamazepine study (N=12) were conducted in healthy subjects to evaluate the effects of CYP3A/P-gp induction and OATP inhibition on the pharmacokinetics of GLE and PIB. In study 1, GLE 300 mg + PIB 120 mg was administered as a single dose either alone, after single and multiple daily doses of rifampin 600 mg, or 24 h after the last rifampin dose. In study 2, GLE 300 mg + PIB 120 mg was administered as a single dose either alone or after multiple doses of carbamazepine 200 mg. Relative to GLE + PIB alone, exposure of GLE was significantly increased by the first co-administered rifampin dose due to OATP inhibition, significantly decreased 24 h after the last rifampin dose due to CYP3A/P-gp induction, and slightly increased when co-administered with steady-state rifampin due to a combination of inhibition and induction forces. Exposure of PIB was not affected when co-administered with the first rifampin dose but was significantly decreased with steady-state rifampin co-administration, or 24 h after the last rifampin dose due to P-gp induction. Carbamazepine significantly decreased GLE and PIB exposure, mainly attributed to P-gp induction. The regimens tested were generally well-tolerated by the subjects and no new safety issues were identified.

The Pituitary Testicular Axis Tolerates Carbamazepine-Gabapentin Adjuvant than Alone Treatment in Male Wistar Rats

Background: Some antiepileptic drugs have been implicated in altering sperm indices and causing sexual dysfunction in males. This study investigated the effects of carbamazepine (CBZ)+garbapentin (GBP) adjuvant treatment on male reproductive functions. Methods: Adult male Wistar rats were selected randomly into four (4) groups of five (5) animals each (n=5). Groups1, 2, 3, and 4 were given; normal saline (0.2 mL), CBZ (25 mg/kg), GBP (50 mg/kg), and 12.5 mg/kg, and 25 mg/kg doses of CBZ and GBP, respectively. The administration was done orally and daily for 56 days. Serum reproductive hormones, oxidative stress markers, and sperm analysis were determined. Histological analysis of the epididymis and testis were done using H and E Results: A significant reduction in the level of follicle-stimulating hormone, Luteinizing Hormone, and testosterone were observed in CBZ and GBP-treated groups. Asignificant increase in lipid peroxidation activities measured by MDA was noticed only in the CBZ-treated group. The level of GSH and catalase increased significantly in the GBP-treated group, while CBZ+GBP treatment increased the level of SOD. The quality and the number of sperm characteristics significantly reduced among the treated animals; this is reflected in the architecture of the testes and epididymis with severe cytoarchitectural distortion, particularly in CBZ treated group, while mild distortion was observed in CBZ+GBP treated group. Conclusion: Adjuvant treatment of CBZ and GBP produces reduced adverse reproductive effects compared with alone treatment.

Understanding the effect of carbamazepine on the recovery of methane from lactic acid wastewater by anaerobic digestion

Anaerobic digestion is a promising technology for recovering methane from organic wastewater and contributing to carbon neutrality in wastewater plants or industrial parks. However, the interference of pharmaceuticals and personal care products with anaerobic digestion is commonly overlooked. Carbamazepine, a typical antiepileptic drug, is frequently detected in sewage sludge, but its influence on anaerobic digestion has not been systematically reported. In this work, the effect of carbamazepine on the anaerobic digestion of lactic acid synthesis wastewater was revealed comprehensively. The results showed that carbamazepine could seriously disturb anaerobic digestion performance, the methane yield decreased from 275.12 to 182.04 mL/g lactic acid as the carbamazepine dosage rose from 0 to 0.14 mM. To better understand how the drug affected anaerobic digestion, model tests were conducted on four stages of hydrolysis, acidification, acetogenesis and methanogenesis. The model tests indicated that such drug could promote the solubilization of inoculum, thereby releasing polysaccharides and proteins. But the hydrolysis stage, commonly recognized as the rate-limiting step was restricted. Meanwhile, the enhanced acidification contributed to the accumulation of volatile fatty acids. Both acetogenesis and methanogenesis were severely disturbed eventually causing a significant decrease in methane yield. The level of interference of carbamazepine on anaerobic digestion was concluded as follows: acetogenesis > methanogenesis > hydrolysis > acidification > solubilization. The high-throughput sequencing revealed the abundance of Chloroflexi increased from 21.5% to 26.7% as a main responsibility for the volatile acid accumulation. The acetoclastic methanogen Methanosaeta decreased from 59.86% to 44.78%, while the hydrogenotrophic methanogens Methanobacterium and Methanomassiliicoccus increased from 28%, 0.5%–37.9% and 4.1%, respectively. Although the recovery of methane was limited for clean production, it was more recommendable to recover the volatile fatty acids from organic wastewater or sludge with high dosage of carbamazepine.

Ultrasound-guided dry needling of masticatory muscles in trigeminal neuralgia - A case series of 35 patients.

Trigeminal neuralgia (TGN) is considered a sensory neuropathy. However, reports of pain on chewing/speaking suggest a masticatory myofascial involvement. To examine the effect of ultrasound-guided dry needling (USGDN), which deactivates myofascial trigger points in masticatory, neck, and facial muscles on TGN symptoms. Charts of 35 patients treated for TGN were retrospectively reviewed. Treatment was USGDN alone or combined with trigeminal ganglion/mandibular nerve pulsed radiofrequency (PRF), followed by yoga mudras to stretch masticatory and facial muscles. Patients were followed for 1-8 years. Outcome parameters were reduction of medications with reduction in neuralgic attack frequency and Numeric Rating Scale (NRS) score. 23 patients (65.7%) received USGDN alone, 12 patients (34.3%) received PRF treatment before USGDN. A significant reduction in the mean (SD) NRS (5.7 [1.2] vs 8.8 [1.6]; P < .001) and neuralgic attack frequency (47 [27] vs 118 [70] attacks/day; P < .001) was seen after PRF compared with baseline, respectively. Following USGDN, the mean (SD) NRS further decreased significantly to 1.0 (0.9) (P < .001). USGDN alone produced a similar improvement in the NRS (8.9 [1.5] at baseline reduced to 0.6 [0.7] post-USGDN; P < .001). Patients in both groups reported a cessation in neuralgic attacks after USGDN. Post-USGDN, 18/27 patients completely discontinued medication, with the mean (SD) carbamazepine dose significantly reducing from 716.7 (260.9) mg/day at baseline to 113.0 (250.2) mg/day post-USGDN (P < .001). Decisive relief of TGN by USGDN suggests neuromyalgia involving masticatory muscles. Prospective, controlled studies could confirm these findings.

Delayed pain relief in patients with trigeminal neuralgia following microvascular decompression: A single-central retrospective study.

Compared to hemifacial spasm after microvascular decompression (MVD), delayed relief (DR) rarely occurs in patients with trigeminal neuralgia (TGN). To analyze the characteristics of post-MVD DR in TGN patients to provide useful clues for the clinical differential diagnosis of postoperative DR. The clinical data of all patients with TGN who underwent MVD in our center from January 1, 2016, to December 31, 2020, were reviewed retrospectively. In 272 TGN MVD patients, DR occurred in nine patients (3.3%) during the follow-up periods of 1-6 years. During surgery, all nine DR-TGN patients were identified as having neurovascular conflicts (NVCs), involving the offending artery (OA) in eight patients (two OAs in two patients) and both an artery and a vein in the other patient. The compression site was near the root entry zone (REZ) in most DR patients (7/9). Delayed relief was relieved in seven patients within 5 days after surgery and within 30 days in the other two patients. No recurrence or serious complications were observed within the mean 4 (1-6)-year follow-up duration. Delayed relief rarely occurs in TGN patients after MVD. Neurovascular conflicts located at the REZ and NVC of grade III may be two important factors contributing to DR in TGN patients. Delayed relief may occur when the pain gradually improves after the operation and responds effectively to a small dose of carbamazepine. The recurrence rate of TGN seems even lower in such patients.

Electrochemical Carbamazepine Aptasensor for Therapeutic Drug Monitoring at the Point of Care.

Monitoring the anti-epileptic drug carbamazepine (CBZ) is crucial for proper dosing, optimizing a patient's clinical outcome, and managing their medication regimen. Due to its narrow therapeutic window and concentration-related toxicity, CBZ is prescribed and monitored in a highly personalized manner. We report an electrochemical conformation-changing aptasensor with two assay formats: a 30 min assay for routine monitoring and a 5 min assay for rapid emergency testing. To enable "sample-to-answer" testing, a de novo CBZ aptamer (K d < 12 nM) with conformational switching due to a G-quadruplex motif was labeled with methylene blue and immobilized on a gold electrode. The electrode fabrication and detection conditions were optimized using electrochemical techniques and visualized by atomic force microscopy (AFM). The aptasensor performance, including reproducibility, stability, and interference, was characterized using electrochemical impedance spectroscopy and voltammetry techniques. The aptasensor exhibited a wide dynamic range in buffer (10 nM to 100 μM) with limits of detection of 1.25 and 1.82 nM for the 5 and 30 min assays, respectively. The clinical applicability is demonstrated by detecting CBZ in finger prick blood samples (<50 μL). The proposed assays provide a promising method to enable point-of-care monitoring for timely personalized CBZ dosing.

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods.

This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150-200 g. Pregnant rats were randomly selected and divided (n= 6) into a control group, low-dose CBZ (10 mg/kg/day) group, medium-dose CBZ (25 mg/kg/day) group, and high-dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2 ) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p< .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

The likelihood approach for potential role of "GABRG2 (C588T, C315T) gene polymorphisms" on the poor response to carbamazepine therapy in Pakhtun population of Pakistan.

Background:Gamma-aminobutyric acid A receptor, gamma 2 gene (GABRG2) encode the GABAA receptor which is responsible for fast neuronal inhibition. Polymorphisms in GABGR2 gene affect the clinical response of anti-epileptic drugs (AEDs). Therefore, we carried out an updated study to find the association GABRG2 gene polymorphisms with carbamazepine (CBZ) non-responsive therapy in the Pakhtun population.Methods:A clinical prospective cohort study was conducted in 79 CBZ treated patients upon consent after the approval of Khyber Medical University Advanced Study and Research Board. Blood sample were taken at optimal dose of CBZ at base line, third and sixth months of the treatment. Blood level of CBZ was measure through reverse phase high performance liquid chromatography (HPLC). Restriction fragment length polymorphisms techniques were used to genotype GABRG2 gene in these patients. CBZ responses were evaluated on three and six months of study by measuring the decrease in frequency of seizure per week.Results:The average maximum dose of CBZ was 455 ± 133 mg/day at baseline, 479 ± 142 mg/day at third month and 495 ± 133 mg/day at sixth month of the treatment. CBZ level was found within therapeutic range (4‐12 mg/L) without any significant (P > .5) variations among the CC, CT and TT genotypes of GABRG2 (C588T and C315T) gene. But the poor clinical response during CBZ treatment was linked (P < .05) with CT and TT genotypes of GABRG2 (C588T and C315T) gene in Pakhtun Population.Conclusion:A poor response to CBZ was found in variant genotypes (CT and TT) of GABRG2 (C588T and C315T) gene in Pakhtun Population.

Insights into the effect of carbamazepine on the anaerobic fermentation of waste activated sludge: Performance, mechanisms and regulation

The effects of pollutants on anaerobic fermentation of waste activated sludge (WAS) have been widely studied. Nevertheless, little attention was paid to how to mitigate the adverse effects of pollutants on anaerobic fermentation. In this work, representative pollutant carbamazepine (CBZ) was chosen to explore the potential effects of CBZ on WAS anaerobic fermentation. Experimental results showed that CBZ at environmental levels slightly promoted the production of short-chain fatty acids (SCFAs), which increased from 3858.2 to 4143.8 mg COD/L as the CBZ dose increased from 8 to 28 mg/kg VSS, but further increasing the CBZ dose to 88 mg/kg VSS decreased the production of SCFAs. Context of homologous group database revealed that the abundance of some functional traits changed, such as RNA processing and modification, energy production and conversion, and amino acid transport. This adverse effect was sustained because CBZ could not be degraded during anaerobic fermentation. Therefore, a regulation strategy was proposed, e.g., persulfate was used to attenuate the toxicity of CBZ to WAS anaerobic fermentation, and the results showed that the removal of CBZ reached 83.7 % in the persulfate-treated reactor. Based on density functional theory and metabolic intermediates determination, hydroxylation and deamination reactions were the two main metabolic pathways for CBZ degradation.

Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.

Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures. A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided. We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200mg/day; lamotrigine, greater than 500mg/day), we encourage consideration of proactive dose reduction at cenobamate 200mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2weeks as dictated by the adverse effects. At cenobamate 200mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy. The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices

Background: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. Methods: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. Results: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). Discussion: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

A Study of Carbamazepine Utilization in the Hospitals in Yogyakarta Special Province

Therapy to control seizures primarily utilizes drugs to date, including carbamazepine. However, carbamazepine has a narrow therapeutic index and is auto-inductive and potential to induce serious adverse reactions, such as Stevens-Johnson Syndrome. This has placed carbamazepine among the priority drugs for which the utilization should be evaluated to ensure safety and effectiveness. This study analyzed the indication, dose, clinical response, and adverse drug reaction (ADR) of carbamazepine by five hospitals in Yogyakarta. The research employed a retrospective cross-sectional design for patients with epilepsy who received carbamazepine for a minimum of 3 days. Patients’ demographics, diagnosis, carbamazepine dose and clinical response, ADR, and concomitant drugs interacting with carbamazepine were collected from medical records during one year of the study. The study involved 78 patients with a majority of male with age of 44.3±13.3 years. The highest indication of carbamazepine was for secondary-type epilepsy (17.95%) with an average maintenance dose of 423.94±135.65 mg/day. Carbamazepine discrepancy was found in absence-type epileptic with an average dose higher than that for other seizure types. Meanwhile, more than 80% seizures could be controlled by carbamazepine monotherapy or its combination. This study found that 16.67% of patients suffered from ADR, particularly a nervous system disorder, with no serious ADR reported. An effective approach is required to improve the appropriateness of antiepileptic drug selection based on the seizure types. In addition, the average maintenance dose of CBZ found in this study, which is relatively lower than those found in studies involving different populations, needs further pharmacogenetic studies of carbamazepine.

Effect of Oral Administration of Valerian Extract at Different Doses on Pharmacokinetic Parameters of Carbamazepine in Rabbits

Carbamazepine (CBZ) is a narrow therapeutic index drug used in the treatment of trigeminal neuralgia and psychiatric disorders. Valerian (VAL) is a popular herbal product which should be prescribed to treat insomnia and anxiety. The study was designed to investigate the presence of significant pharmacokinetic (PK) interaction between Valerian (VAL) at different concentrations on Carbamazepine (CBZ) pharmacokinetic parameters in healthy male rabbits. In an in vivo, parallel-randomized controlled trial, the rabbits in three groups "first (control), second and third" were given oral doses of CBZ (50 mg/kg), for "second and third" groups (as test groups) rabbits were given (20 and 40 mg/kg/day) of the VAL respectively, as suspension in normal saline for eight consecutive days. On the eighth day, CBZ was co-administered an hour after adding the last dose of VAL suspension. Venous blood samples (1.0-1.5 mL) were obtained from rabbits' ears' marginal vein at predetermined different periods. The plasma of this blood separation was done using centrifugation and stored at -80°C, prior to analysis by using CBZ chemiluminescent enzyme immunoassay detection kit. Different PK parameters such as Cmax, tmax, t½, ke, AUC0-24 and AUC0-∞ were determined for the three groups, applying Statistical testing (ANOVA). The results showed statistical insignificant differences for all PK parameters among the three groups with (p˃0.05). The findings showed that VAL at both concentrations is not likely to interfere with PK parameters related to CBZ, Further confirmation in humans shoud be done before these findings are applied to patient care.

Eslicarbazepine, but Not Lamotrigine or Ranolazine, Shows Anticonvulsant Efficacy in Carbamazepine-Resistant Rats Developed by Window-Pentylenetetrazole Kindling.

Approximately 30% of epileptic patients develop Drug-Resistant Epilepsy. Based on evidence that shows a loss of efficacy in some sodium channel blocker antiseizure drugs in epilepsy, we focus our study on assessing the anticonvulsant efficacy of different sodium channel blockers on carbamazepine (CBZ)-resistant seizures generated using the window-pentylenetetrazole (PTZ) kindling model to verify whether one of these drugs presents some anticonvulsant effect that could have potential therapeutic use. Wistar rats were treated with a subthreshold dose of PTZ (35 mg/kg) three times/week. Fully kindled rats were then treated with a single dose of CBZ (40 mg/kg i.p.) at 2, 9 and 16 days after their last kindling stimulation to obtain CBZ-resistant rats. Right after, sodium channel blockers were tested for anticonvulsant action (lamotrigine, 30 mg/kg i.p.; eslicarbazepine, 150 or 300 mg/kg i.p.; ranolazine, 10, 20 or 40 mg/kg i.p.). Behavioral parameters included severity, latency or duration of convulsions. Our data showed for the first time directly that eslicarbazepine does have an anticonvulsant effect over CBZ-resistant seizures, while lamotrigine shows drug resistance and ranolazine demonstrates severe seizure worsening. It is of potential therapeutic relevance that eslicarbazepine could be useful to control seizures resistant to common sodium channel blockers such as CBZ.

Autologous conditioned serum (Orthokine) injection for treatment of classical trigeminal neuralgia: results of a single-center case series

BackgroundDespite some advances, treatment of trigeminal neuralgia remains a significant challenge. This study determines the efficacy and safety of autologous conditioned serum (Orthokine) injection into the foramen oval to treat refractory trigeminal neuralgia.Case presentationThis is a consecutive case series from the Pain and Palliative Care Department of Imam Reza University Hospital, Tabriz, Iran. Eleven Iranian patients, eligible according to the inclusion and exclusion criteria, aged 45.64 ± 11.58 years (Four male and seven female, all Iranian) with established classical trigeminal neuralgia were injected with Orthokine (2 mL per injection) once a week for three consecutive weeks (total of four injections). Numeric rating scale scores for facial pain intensity and also carbamazepine daily dose were confirmed at pretreatment (T0) and at week 1 (T1), week 2 (T2), week 3 (T3), week 4 (T4), and month 2 (T5) posttreatment. Pain intensity was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (8.18 ± 1.99 to 2.82 ± 2.13, p < 0.001), an effect that was retained at week 4 (T4) and month 2 (T5) follow-ups (2.82 ± 2.13 to 3.36 ± 2.69, p = 0.886). Carbamazepine consumption was significantly reduced in the first 3 weeks of follow-up in comparison with baseline (T0 to T3) (636.36 ± 307.48 to 200.00 ± 296.64, p = 0.003), an effect that was retained at week 4 and month 2 follow-ups (200.00 ± 296.64 to 200.00 ± 282.84, p = 0.802). There were no serious adverse events in participants.ConclusionOrthokine injection led to consistent pain relief and reduced carbamazepine dosage in patients with trigeminal neuralgia, with acceptable safety.

Therapeutic drug monitoring in epilepsy: Can drug levels reliably measure drug adherence?

Background: Drug adherence is often assessed from patients' reports and confifirmed with therapeutic drug monitoring. The study investigated the relationship between reports of drug adherence and drug levels of carbamazepine among adult patients on carbamazepine monotherapy. Methods: 84 consecutively consenting patients who had been on carbamazepine monotherapy for seizure control were recruited from the Neurology Clinic, LUTH, Idi-Araba, Lagos for the study. Adherence in the past month was assessed using a standard proforma. Drug levels were taken in the trough phase (just before the next dose of carbamazepine) and analyzed using high performance liquid chromatography. Results: Among the population studied, full adherence was reported in 45.2% of the participants while the remainder had missed one or more doses in the past month. Serum drug levels were found to be signifificantly higher in patient who reported full adherence compared to non-adherent patients (p&lt;0.05). When levels were compared to the reference range of carbamazepine, 15.8% of the patient who reported good adherence had blood levels in the subtherapeutic range, while 21.7% who reported poor adherence had blood levels in the subtherapeutic range (p&gt;0.05). Conclusion: Adherence is associated with higher drug levels, but both adherent and nonadherent patients had a similar likelihood of having serum drug blood levels in the subtherapeutic range. This calls for caution in the interpretation of drug levels as it relates to adherence. Further studies on standardization of therapeutic drug measurement to develop predictive tools for adherence are recommended.