Serum Carbamazepine Research Articles

Audit on monitoring physical health of patients on mood stabilisers following NICE guidelines

AimsThe aim is to find out if the physical health monitoring is adhered to in accordance with NICE guidelines in individuals with Intellectual disability who are on mood stabilisers and known to LD services.MethodWe sought to explore if the physical health monitoring for prescribing mood stabilisers in a sample of people with ID was consistent with good practice guidelines.We collected the data by reviewing the clinical records of individuals with LD who were under the care of mental health services in the CLDT- Wrexham and prescribed a mood stabiliser drug. We also contacted the patient's carers who came to outpatients and by calling the GP surgery and enquiring about the details. We also assessed the Welsh clinical portal in order to assess the blood tests.Data were collected by trainee doctors in Psychiatry. This was a retrospective audit, looking at data from Learning Disability psychiatry caseload. We identified about 16 patients on mood stabilisers.ResultPhysical health monitoring for prescribing mood stabilisers was almost consistent with good practice guidelines. This has shown that the majority of the monitoring has complied. There are few lacunae, such as Thyroid function not being monitored every 6 months for patients on Lithium, Serum Carbamazepine levels not being monitored as per guidelines with 1 patient not having blood done at all whilst on Carbamazepine. Moreover, the details are not readily available for the Consultant/ team when needed, thus making it very tedious for them to search/ contact the GP, etc.ConclusionMedications such as mood stabilisers can increase the risk further if the patient's physical health is not monitored regularly. This can lead to compromised quality of life for the patient and in some cases increased morbidity. Hence we have come up with a proforma that can be attached to patient case notes. This will serve as a record for us and prompt for physical monitoring. We will keep a database online with reminders set. This is to ensure a continuity of care for the patients.

Therapeutic monitoring of carbamazepine and its active metabolite during the 1st postnatal month: Influence of drug interactions

ObjectiveTo receive information about carbamazepine and its active metabolite 10,11-epoxide transport into mature milk and suckling infants. MethodsIn this cohort study, maternal serum, mature milk, and infant serum carbamazepine and epoxide levels were measured between the 6th and 29th postnatal day (carbamazepine in 1990–2017, epoxide in 1997–2017). Paired maternal serum, infant serum and milk levels were used for the assessment of ratios of this levels. The influence of combined treatment with enzyme-inducing antiepileptic drugs and valproic acid was assessed. Relationship between maternal serum, infant serum, and milk levels was also evaluated. ResultsMaternal carbamazepine levels were 1.4–10.4 mg/L, milk 0.5–6.7 mg/L and infant 0.5–2.6 mg/L. Maternal 10,11-epoxide levels were 0.3–5.4 mg/L, milk 0.3–3.7 mg/L and infant 0.3–0.6 mg/L. Highly significant correlations were observed exclusively between milk and maternal serum levels of both carbamazepine and 10,11-epoxide. Concomitant administration of enzyme-inducing antiepileptic drugs significantly increased the maternal apparent oral clearance of carbamazepine by approximately 130%. Carbamazepine combined with valproic acid significantly increased epoxide levels in milk and maternal serum but not in breastfed infants. ConclusionsIn breastfed infants, carbamazepine levels did not reach the lower limit of the therapeutic range used for the general epileptic population, and the majority of epoxide levels were less than the lower limit of quantification. Routine monitoring of carbamazepine in these infants is not compulsory. However, observation of breastfed infants is desirable. If signs of potential adverse reactions are evident, infant serum concentrations should be monitor.

Effects of antiepileptic drugs on serum lipids profile among young adult Sudanese patient with epilepsy at Aljazeera State

consequences that lead to an increase in risk of atherosclerosis in patients with epilepsy, several studies have reported that the patients commonly used antiepileptic drugs like phenytoin, and carbamazepine increase serum total Cholesterol, High Density Lipoproteins Cholesterol (HDL-C) Low Density lipoprotein Cholesterol ( LDL-C ) levels and Triglyceride (TG) .The aim of this study to assess and compare serum lipid profile of young adult patients treated by anti-epileptic drugs (phenytoin, oxcarbazepine and valproic acid) . Materials and Methods a cross-sectional study was conducted in Aljazeera state. Epileptic patients were of recruited. and taking antiepileptic drugs for more than six months and on regular follow up; approximately 120 patients on commonly used antiepileptic drugs (40 on phenytoin, 40 on oxcarbazepine, 40 on valproic Acid). Age and sex matching 40 controls were taken. our results show significant difference in the of mean TC, TG, HDL, and LDL-C levels in the group receiving phenytoin for more than six months when compared with control group P value (0.00) for all lipid profile. Also significant difference between the mean of TC, TG, HDL-C and LDL-C levels in the group receiving oxcarbazepine for more than six months when compared with control P value (0.00 ) for all lipid profile. From the present study we concluded that CYP enzyme inducer anti-epileptic medicines like phenytoin and oxcarbazepine is strongly associated with increased levels of TC, LDL-C, HDL-C and TG, where asvalproate showed no significant change. Therefore, the serum cholesterol level should be regularly monitored in patients undergoing. Therapy with inducer anti-epileptic medicines.

Measuring the appropriateness of carbamazepine and valproic acid prescribing and utilization using a newly implemented online system in the Tabuk Region of Saudi Arabia

Epilepsy is a common neurologic disorder, which is efficiently treated with carbamazepine and valproic acid. Moreover, Saudi Ministry of Health implemented a new E-system for Poison Control Centers called Awtar to enhance technology utilization in ensuring patients’ satisfaction and to improve treatment outcomes. Therefore, we conducted this study to assess appropriateness of indication of requests and therapeutic levels of carbamazepine and valproic acid in Tabuk area, North West Saudi Arabia. This is a retrospective observational study conducted in Poison Control & Forensic Chemistry Center, Tabuk, Saudi Arabia. Patients’ data were obtained for years 2018 and 2019. The blood levels of carbamazepine and valproic acid were measured by Therapeutic Drug Monitoring (TDM) Unit. We selected patients treated with either valproic acid or carbamazepine alone without any history of drug allergy. Data of 264 patients were extracted from Awtar E-system. Serum carbamazepine levels were within therapeutic range in 114 patients (75.50%), above-therapeutic range in 13 patients (8.61%) and sub-therapeutic levels in 24 patients (15.89%). Regarding serum valproic acid, it is within therapeutic range in 62 patients (54.87%), above-therapeutic range in 11 patients (9.73%) and sub-therapeutic levels in 40 patients (35.40%). In conclusion, this study gives information about partial appropriateness of usage of carbamazepine and low level of appropriateness of valproic acid. However, more efforts are needed to improve results of appropriateness of indication of antiepileptic drugs.

Plasmonic biosensor based on an effective medium theory as a simple tool to predict and analyze refractive index changes

Surface plasmon resonance was used for the detection of different kinds of organic molecules, which was achieved employing a Kretschmann configuration. A simple theoretical model based on effective medium theory was used for estimation of the SPR angle. The employed model considers an effective refractive index, which has some advantages in comparison to other effective medium theories. This model depends on the surface coverage, size of the sample and also considers the scattering by molecules deposited on the surface of the thin film. Using an effective refractive index as a tool to predict the behavior of the SPR signal offers a significant advantage for the development of new biosensors, providing a deeper physical insight on the behavior of such phenomena, since inferring the behavior of SPR signals is of great importance for chemical analysis and bio-sensing. Therefore, in this work, an effective medium model was compared with experimental SPR measurements as a function of angle incidence of different molecules deposited onto thin films, specifically Bovine Serum Albumin (BSA) and carbamazepine attached to BSA, in order to validate the theoretical model. Evaluation of the proposed model for SPR signal was in good agreement with the experimental results. Statistical tests were obtained, with a 99% of correlation between the experimental data and the theoretical predictions around the resonance.

Early Chronic Carbamazepine-in-Food Administration to MAM/Pilocarpine Rats Does Not Affect Convulsive Motor Seizures.

Antiepileptic drug-resistance is a major health problem in patients with cortical dysplasia (CD). Whether drug-resistant epilepsy is associated with progressive brain damage is still debated. We previously generated a rat model of acquired CD, the methylazoxymethanol-pilocarpine (MP) rat, in which the occurrence of status epilepticus and subsequent spontaneous seizures induce progressive brain damage (Nobili et al., 2015). The present study tested the outcome of early-chronic carbamazepine (CBZ) administration on both seizure activity and brain damage in MP rats. We took advantage of the non-invasive CBZ-in-food administration protocol, established by Ali (2012), which proved effective in suppressing generalized convulsive seizures in kainic acid rat model of epilepsy. MP rats were treated immediately after the onset of the first spontaneous seizure with 300 mg/kg/day CBZ formulated in pellets for a two-months-trial. CBZ-treated rats were continuously video-monitored to detect seizure activity and were compared with untreated epileptic MP rats. Despite CBZ serum levels in treated rats were within the suggested therapeutic range for humans, CBZ affected spontaneous convulsive seizures in 2 out of 10 treated rats (responders), whereas the remaining animals (non-responders) did not show any difference when compared to untreated MP rats. Histological analysis revealed cortical thinning paralleled by robust staining of Fluoro-Jade+ (FJ+) degenerating neurons and diffuse tissue necrosis in CBZ-non-responder vs CBZ-responder rats. Data reported here suggest that MP rat model represents suitable experimental setting where to investigate mechanisms of CD-related drug-resistant epilepsy and to verify if modulation of seizures, with appropriate treatment, may reduce seizure-induced brain damage.

Development and Validation of a Free Carbamazepine Assay on an Automated Chemistry Analyzer.

Carbamazepine is an effective drug for treating seizures and trigeminal neuralgia. Therapeutic drug monitoring of free carbamazepine in serum can be useful in situations that drug--protein binding is altered to guide regimen adjustment and to aid in the diagnosis of clinical toxicity. Separation of the nonprotein bound carbamazepine was achieved via ultrafiltration through a molecular weight cut-off filter. A method for free carbamazepine measurement was developed on the automated cobas chemistry analyzers (Roche Diagnostics) by modifying the Carbamazepine Gen 4 assay (Roche Diagnostics). Assay performance characteristics were established including precision, accuracy, reportable range, analytical specificity, and stability. The intra- and inter-assay imprecision was 0%-1.4% and 2.4%-5.1%, respectively. The lower limit of quantitation was 0.3 µg/mL, and the assay was linear up to 10.0 µg/mL. A spike recovery study, using reference standard material, showed recovery was 93.5%--101.3% across the analytical measurement range. Method comparison with a reference laboratory method demonstrated equivalent performance with a slope of 1.01, intercept of 0.09, and correlation coefficient of 0.9948. This assay provides a simple and accurate method for monitoring free carbamazepine with a fast turnaround time.

Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients

Effect of CYP3A5 genotypes on serum carbamazepine concentrations at steady-state in Vietnamese epileptic patients

Use of Charcoal Hemoperfusion and High-Flux Hemodialysis in Carbamazepine Intoxication: Two Case Reports

Introduction: Carbamazepine (CBZ) is a drug used in the treatment of neurological and psychiatric disorders. Intoxication with CBZ is a serious condition that can result in coma, hemodynamic instability and death. Urgent management of CBZ intoxication is life saving and extracorporeal methods are used for removal of CBZ. It is also known that CBZ is highly protein-bound and charcoal hemoperfusion is the most effective extracorporeal elimination. We know that hemodialysis is also a technique for management of this drug. Case Presentation: We present two cases of CBZ intoxication, treated with two different methods, charcoal hemoperfusion and high-flux hemodialysis. The first patient who was receiving CBZ treatment for anxiety disorder was admitted to Bakirkoy Dr. Sadi Konuk Educational and Research Hospital, Istanbul, Turkey on 11th of December 2017, with complaints of dizziness and blurred vision. Vital signs were stable. Laboratory tests were normal. Serum CBZ level was 56 μg/mL (reference 4 - 12 μg/mL). The CBZ level was 15.6 μg/mL after charcoal hemoperfusion for 3 hours. The second patient was admitted to the emergency room on the 5th of February 2015, with blurred consciousness. The patient had taken CBZ for suicide. The CBZ level was 33 μg/mL and was 14.86 μg/mL after hemodialysis with high-flux membrane for 4 hours. Serum CBZ level decreased by 73% in the first patient who received charcoal hemoperfusion and by 55% in the second patient who received high-flux hemodialysis. Conclusions: In presenting these cases, we aimed to show the decrease of CBZ serum levels by using two different hemodialysis modalities in CBZ intoxication.

Peripheral and central auditory function in adults with epilepsy and treated with carbamazepine

Purpose of the study: Epilepsy is a chronic medical disease in one third of patients. Chronic epilepsy and its antiepileptic drugs (AEDs) therapy are commonly associated with comorbid adverse somatic conditions. This study aimed to evaluate auditory function in patients with idiopathic epilepsy and on treatment with carbamazepine (CBZ).Methods: This is a cross-sectional case-control study. It included 50 patients with idiopathic epilepsy (mean age = 34.56 ± 7.11 and duration of illness = 17.84 ± 7.21years) and 40 healthy subjects. Hearing was evaluated using pure tone audiometry and brainstem auditory evoked potentials (BAEPs) analyses.Results: Mild bilateral hearing impairment and abnormal acoustic reflex (but normal tympanometry) were reported in more than one third of patients. Compared to controls, BAEPs of patients had prolonged waves I, III, V latencies and I–III, III–V and I–V interpeak latencies (IPLs) particularly at high repetition frequencies. Significant correlations were identified between CBZ dose, serum level and duration of treatment with waves I, III and V and I–III, III–V and I–V latencies at high repetition frequencies.Conclusions: Long-term treatment with CBZ may result in delayed auditory conduction within the peripheral pathways and brainstem. This should be taken into account during drug selection and monitoring of patients with epilepsy.

A novel sensitive and selective electrochemical sensor based on integration of molecularly imprinted with hollow silver nanospheres for determination of carbamazepine

An electrochemical sensor based on hollow silver nanospheres (hAgNS) and molecularly imprinted polymer (MIP) was developed for drug analysis by using carbamazepine (CBZ) as a model analyte. hAgNS, serving as a support material for MIP immobilization, possesses large accessible surface area with superb electric conductivity, while electrochemically synthesized MIP film warrants improved selectivity for CBZ. Quantification based on the “MIP/gate effect” was performed by employing Fe(CN)63−/4− as the probe to indicate the current intensity. The sensor materials were characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under the optimal conditions, a linear relationship of the electrical signal versus the concentration of CBZ was obtained in the range from 8.0 × 10−11 to 6.0 × 10−8 M with a detection limit of 3.2 × 10−11 M (S/N = 3). Moreover, the prepared sensor exhibited specific detection of CBZ over its structural analogues and interferents, and the established electrochemical method was validated using the standard method-high performance liquid chromatography (HPLC). Eventually, rapid and accurate determination of CBZ in rat serum and cell samples was carried out after easy sample pretreatment.

Effects of CYP3A5 and UGT2B7 variants on steady-state carbamazepine concentrations in Chinese epileptic patients.

Carbamazepine (CBZ) is a widely used antiepileptic drug with large interindividual variability in serum concentrations. Previous studies found that CYP3A5∗3 (rs776746), UGT2B7∗2 (802C>T), and UGT2B7∗3 (211G>T) variants could change the enzymes’ activity, which may influence drug concentrations. Our study aims to investigate whether these variants affect steady-state CBZ concentrations in Chinese epileptic patients. In our study, 62 epileptic patients who received CBZ as monotherapy were monitored for steady-state CBZ concentrations. We used polymerase chain reaction (PCR)-based Sanger sequencing to assess the variants CYP3A5∗3, UGT2B7∗2, and UGT2B7∗3. The results showed a positive correlation between dose and CBZ serum concentration in all patients and in patients with 3 different variants (all P < .05). After CBZ concentrations were normalized by the dose administered, negative correlations between dose-normalized CBZ concentrations and CBZ doses were observed in all patients, and in CYP3A5∗3 and UGT2B7∗3 patients (all P < .05), but not in UGT2B7∗2 patients (P = .1080). UGT2B7∗2 patients exhibited lower dose-normalized CBZ concentrations and larger CBZ dose requirements than UGT2B7∗1/∗1 patients (P = .0139, P = .032, respectively). There were no differences between UGT2B7∗3, UGT2B7∗1/∗1 and CYP3A5∗3, and CYP3A5∗1/∗1 patients with regard to steady-state CBZ concentration, dose-normalized concentration, required CBZ dose, and body weight-normalized dose (all P > .05). Moreover, a significant difference in body weight-normalized CBZ dose between UGT2B7 GC and TT haplotype patients was observed (P = .0154). In conclusion, our study found that the UGT2B7∗2 variant, but not the CYP3A5∗3 or UGT2B7∗3 variant, could affect steady-state CBZ concentrations in epileptic patients.

Carbamazepine, a beta-cell protecting drug, reduces type 1 diabetes incidence in NOD mice

Pancreatic beta-cells are selectively destroyed by the host immune system in type 1 diabetes. Thus, drugs that preserve beta-cell mass and/or function have the potential to prevent or slow the progression of this disease. We recently reported that the use-dependent sodium channel blocker, carbamazepine, protects beta-cells from inflammatory cytokines in vitro. Here, we tested the effects of carbamazepine treatment in female non-obese diabetic (NOD) mice by supplementing LabDiet 5053 with 0.5% w/w carbamazepine to achieve serum carbamazepine levels of 14.98 ± 3.19 µM. Remarkably, diabetes incidence over 25 weeks, as determined by fasting blood glucose, was ~50% lower in carbamazepine treated animals. Partial protection from diabetes in carbamazepine-fed NOD mice was also associated with improved glucose tolerance at 6 weeks of age, prior to the onset of diabetes in our colony. Less insulitis was detected in carbamazepine treated NOD mice at 6 weeks of age, but we did not observe differences in CD4+ and CD8+ T cell composition in the pancreatic lymph node, as well as circulating markers of inflammation. Taken together, our results demonstrate that carbamazepine reduces the development of type 1 diabetes in NOD mice by maintaining functional beta-cell mass.

Determination of carbamazepine and 10-hydroxy-carbamazepine in human serum by solid-phase extraction with poly ethylene glycol dimethacrylate monolithic column coupled with high performance liquid chromatography

A polymeric monolithic solid phase extraction sorbent was fabricated from sole ethylene glycol dimethacrylate in a syringe and applied as a sorbent for the determination of carbamazepine (CBZ) and 10-hydroxy-carbamazepine (MHD) in human serum using high performance liquid chromatography. The effects of reaction temperature and reaction time on the extraction performance of the target compounds were investigated. The parameters, such as washing solvent, and elution solution and its volume, were optimized. Under the optimized condition, the purification and enrichment of CBZ and MHD in human serum were successfully achieved on the proposed poly ethylene glycol dimethacrylate (EDMA) monolithic column. The linear ranges were 0.02-40 μg/mL for CBZ and 0.05-100 μg/mL for MHD. The results indicated that the method exhibited good linearity in the corresponding ranges with the correlation coefficients (r) of 0.999. The limits of detection (S/N=3) of CBZ and MHD were 0.004 μg/mL and 0.01 μg/mL, respectively. The average recoveries at three spiked levels of CBZ and MHD were 92.7% and 94.2%, respectively, with relative standard deviations (RSDs) ≤ 6.1%. Furthermore, the intra column to column (n=3) and inter batch to batch (n=5) RSDs were no more than 5.3%. The RSDs of eight repeated extraction cycles were no more than 5.8%. The developed method is effective and simple, and is suitable for the determination of CBZ and MHD in human serum.

An LC-MS/MS based candidate reference method for the quantification of carbamazepine in human serum

A validated LC-MS/MS-based candidate reference measurement procedure for the quantification of carbamazepine is presented in order to be used for standardization and harmonization of routine assays applied for therapeutic drug monitoring. Sample preparation was based on protein precipitation using acetonitrile followed by sample dilution. Since the previously listed certified reference material (CRM) SRM 1599 (anticonvulsant drug level assay standard) is no longer available, an ISO certified calibration material was used in this assay. As internal standards deuterated analyte congeners were applied. The method allows the measurement of carbamazepine, carbamazepine-10,11-epoxide and 10-hydroxy-10,11-dihydrocarbamazepine in the concentration range of 0.1 to 22.0μg/ml with LODs and LOQs of <0.1μg/ml and 0.1μg/ml, respectively. Comparative measurement of 105 native patient samples using the here presented method showed a good agreement between two independent laboratories with a mean bias of 0.6%.

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD50 value of sulforaphane in mice was estimated at 212.67mg/kg, while the TD50 value – at 191.58mg/kg. In seizure tests, sulforaphane at the highest dose tested (200mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6Hz-induced psychomotor seizure. At doses of 10–200mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300mg/kg), hypothermia (at 150–300mg/kg), impairment of motor coordination (at 200–300mg/kg), decrease in skeletal muscle strength (at 250–300mg/kg), and deaths (at 200–300mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200mg/kg. In conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients should be further evaluated.

Correlation Between Elimination Parameters of Phenytoin and Carbamazepine in Patients with Epilepsy Receiving Both Drugs Concomitantly: A Preliminary Study

An individualized dosage regimen is of importance for phenytoin and carbamazepine therapy. However, not all patients can afford the cost of therapeutic drug monitoring, particularly in rural areas. An approach used to assist individualized drug therapy is needed. The aim of the study was to determine the relationship between maximum rate of metabolism of phenytoin and carbamazepine clearance. Such information will be beneficial in aiding individualized drug therapy. Thirteen epileptic patients receiving phenytoin in combination with carbamazepine were included in the study. All patients were studied at steady-state conditions with no change in phenytoin and carbamazepine dosage for at least one month before the study commencement. Serum phenytoin and carbamazepine concentrations were determined by Fluorescence Polarization Technique (TDx® Analyzer System). The maximum rate of metabolism of phenytoin (V max) and carbamazepine clearance (CLCBZ ) was calculated based on measured drug levels at steady-state. Subsequently, their relationships were determined by simple linear regression. There was a high correlation coefficient between maximum rate of metabolism of phenytoin (V max) and carbamazepine clearance (CLCBZ) [r = 0.816; p = 0.001 and r = 0.818; p = 0.001 for V max (mg/day) vs. CLCBZ (L/day) and V max (mg/kg/day) vs. CLCBZ (L/kg/day), respectively]. This high positive correlation can be of use in predicting V max from CLCBZ and vice versa, particularly in rural hospitals in Thailand where therapeutic drug monitoring for either one of the drugs is not available. Elimination parameters of phenytoin and carbamazepine can be predicted by their respective relationships. The proposed equations used to determine maximum rate of metabolism of phenytoin and carbamazepine clearance are of benefit in reducing the cost for drug concentration measurements.

Interference-free Determination of Carbamazepine in Human Serum Using High Performance Liquid Chromatography: A Comprehensive Research with Three-way Calibration Methods.

In the present study, a comprehensive and systematic strategy was described to evaluate the performance of several three-way calibration methods on a bio-analytical problem. Parallel factor analysis (PARAFAC), alternating trilinear decomposition (ATLD), self-weighted alternating trilinear decomposition (SWATLD), alternating penalty trilinear decomposition (APTLD), and unfolded partial least squares combined with the residual bilinearization procedure (U-PLS/RBL) were applied on high performance liquid chromatography with photodiode-array detection (HPLC-DAD) data to quantify carbamazepine (CBZ) in different serum samples. Using the proposed approach, successfully quantification of CBZ in human plasma, even in the presence of diverse uncalibrated serious interfering components was achieved. Moreover, the accuracy and precision of each algorithm for analyzing CBZ in serum samples were compared using root mean square error of prediction (RMSEP), the recovery values and figures of merits and reproducibility of the analysis. Satisfying recovery values for the analyte of interest were obtained by HPLC-DAD on a Bonus-RP column using an isocratic mode of elution with acetonitrile/K2HPO4 (pH = 7.5) buffer solution (45:55) coupled with second-order calibrations. Decreas of the analysis time and less solvent consumption are some of the pluses of this method. The analysis of real samples showed that the modeling of complex chromatographic profiles containing CBZ as the target drug using any of the mentioned algorithms can be potentially benefit drug monitoring in therapeutic research.

Determination of serum carbamazepine concentration using dried blood spot specimens for resource-limited settings

ABSTRACTObjectives: Carbamazepine (CBZ) is a commonly used anti-epileptic in rural hospitals in India. These hospitals lack the facilities to measure CBZ concentration; however, in larger hospitals this is performed using high performance liquid chromatography (HPLC). Dried blood spot (DBS) represents a feasible matrix for safe transportation by post/courier. This study was to determine whether the concentration of CBZ in serum can be predicted from that measured in DBS using an inexpensive HPLC method and inexpensive standard filter paper.Methods: CBZ in serum and DBS from 80 epileptic patients were measured using a validated HPLC assay. The data was then randomly divided into two groups; simple Deming regression was performed with the first group and validation was performed using the second.Results: There was a good correlation between the serum and DBS concentrations (r = 0.932) in the first group. The regression equation obtained was: predicted serum concentration = DBS concentration x 0.83 + 1.09. In the validation group, the correlation between the predicted and actual serum concentrations was also good (r = 0.958), and the mean difference between them was only 0.28 μg/ml (p = 0.8062). The imprecision and bias in both the groups were acceptable.Conclusion: Using inexpensive materials, serum CBZ concentrations can be accurately predicted from DBS specimens. This method can be recommended for the therapeutic drug monitoring of CBZ in resource-limited settings.

The effect of carbamazepine on etonogestrel concentrations among contraceptive implant users

Objectives: Carbamazepine (CBZ), a known cytochrome P-450 enzyme inducer, significantly reduces serum hormone levels from oral contraceptives. Despite case reports of contraceptive failure with concomitant use of the etonogestrel (ENG) contraceptive implant and CBZ, no studies have explored the pharmacologic relationship between CBZ and systemic contraceptives. We set out to investigate the pharmacokinetic and pharmacodynamic effects of CBZ on the ENG implant. Methods: We enrolled healthy, reproductive-aged women who had been using an ENG implant for 1–3 years. We collected a serum ENG level at baseline and after 3 weeks of coadministered CBZ titrated up to 300 mg twice daily. A serum CBZ level confirmed study compliance. To measure ENG, we used a liquid chromatography-tandem mass spectrometry assay. We compared ENG concentrations before and after CBZ exposure with the Wilcoxon-signed rank test. We evaluated pharmacodynamic effects of CBZ exposure by measuring ovarian follicle-like structures and endometrial thickness. Results: We enrolled 13 women, and 10 were study compliant. Participants had a mean age of 25.6 years (±5.6), average BMI of 30.4 (±7.3) and median duration of implant use of 23 months (range 15–35). The median ENG levels before and after CBZ use were 158.1 pg/mL (range: 127.9–347.3) and 50.9 pg/mL (range: 39.4–202.3), respectively (p=.005). Some 80% of participants had ENG levels below the threshold for ovulatory suppression (<90 pg/mL) after CBZ exposure. We did not identify pharmacodynamic changes. Conclusions: Our study provides evidence that women using an ENG implant while taking CBZ have significant reductions in their ENG levels. Our findings strongly suggest that the ENG implant will be less effective for women taking CBZ.