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PURPOSE: The purpose of this study was to evaluate the effect of UGT1A4 and UGT2B7 polymorphisms on the plasma concentration of lamotrigine in Chinese patients with bipolar disorder. METHODS: A total of 104 patients were included in this study. Steady-state plasma lamotrigine concentrations were determined in each patient after at least 21â days of continuous treatment with a set dose of the drug. Lamotrigine plasma concentrations were ascertained using ultra-performance liquid chromatography. Simultaneously, plasma samples were used for patient genotyping. RESULTS: The age, sex, BMI, daily lamotrigine dose, plasma lamotrigine concentration, and lamotrigine concentration/dose ratio of patients exhibited significant differences, and these were associated with differences in the genotype [UGT1A4 -142T>G and UGT2B7 -161C>T (Pâ <â 0.05)]. Patients with the GG and GT genotypes in UGT1A4 -142T>G had significantly higher lamotrigine concentration/dose values (1.6â ±â 1.1 and 1.7â ±â 0.5â µg/ml per mg/kg) than those with the TT genotype (1.4â ±â 1.1â µg/ml per mg/kg). Likewise, patients with the UGT2B7 -161C>T TT genotype had significantly higher lamotrigine concentration/dose values (1.6â ±â 1.1â µg/ml per mg/kg) than those with the CC genotype (1.3â ±â 1.3â µg/ml per mg/kg). Multiple linear regression analysis showed that sex, lamotrigine dose, UGT1A4 -142T>G, and UGT2B7 -161C>T were the most important factors influencing lamotrigine pharmacokinetics (Pâ <â 0.001). CONCLUSION: The study results suggest that the UGT1A4 -142T>G and UGT2B7 -161C>T polymorphisms affect lamotrigine plasma concentrations in patients with bipolar disorder.
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OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1⯱â¯328.1â¯ng/mL, in contrast to the CC phenotype at 334.0⯱â¯161.1â¯ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1â¯G TT and CYP3A4×10 GC groups, with rates of 77.8â¯% (7 of 9 patients) and 50.0â¯% (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1â¯G TT and CYP3A4×10 CC groups, recorded at 11.1â¯% (1 of 9 patients) and 10.0â¯% (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with pâ¯<â¯0.05). We suggest a plasma concentration range of 625-900â¯ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.
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Anticonvulsivantes , Citocromo P-450 CYP3A , Epilepsia , Nitrilas , Piridonas , Humanos , Citocromo P-450 CYP3A/genética , Criança , Feminino , Masculino , Piridonas/farmacocinética , Piridonas/uso terapêutico , Piridonas/sangue , Epilepsia/tratamento farmacológico , Epilepsia/genética , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Nitrilas/farmacocinética , Pré-Escolar , Adolescente , Polimorfismo Genético/genética , China , Povo Asiático/genética , Genótipo , Resultado do Tratamento , População do Leste AsiáticoRESUMO
PURPOSE: We aimed to investigated the influencing risk factors of voriconazole-induced liver injury in Uygur pediatric patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: This was a prospective cohort design study. High-performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentration. First-generation sequencing was performed to detect gene polymorphisms. Indicators of liver function were detected at least once before and after voriconazole therapy. RESULTS: Forty-one patients were included in this study, among which, 15 patients (36.6%) had voriconazole-induced liver injury. The proportion of voriconazole trough concentration > 5.5 µg·mL-1 patients within the DILI group (40.0%) was significantly higher compared to the control group (15.4%) (p < 0.05). After administration of voriconazole, the values of ALT (103.3 ± 80.3 U/L) and AST (79.9 ± 60.6 U/L) in the DILI group were higher than that in the control group (24.3 ± 24.8 and 30.4 ± 8.6 U/L) (p < 0.05). There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2, CYP2C19*3, CYP2C19*17, and UGT1A4 (rs2011425) (p > 0.05). CONCLUSION: There was a significant correlation between voriconazole-induced liver injury and voriconazole trough concentration in high-risk Uygur pediatric patients with allogeneic HSCT.
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Antifúngicos , Doença Hepática Induzida por Substâncias e Drogas , Transplante de Células-Tronco Hematopoéticas , Voriconazol , Humanos , Voriconazol/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Masculino , Feminino , Estudos Prospectivos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Fatores de Risco , Antifúngicos/efeitos adversos , Pré-Escolar , China , Adolescente , Citocromo P-450 CYP2C19/genética , Transplante Homólogo/efeitos adversosRESUMO
PURPOSE: This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. RESULTS: The plasma concentration showed a linear correlation with the daily dose taken ( r â =â 0.17; P â <â 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5â ±â 297.1 vs. 633.8â ±â 305.5â µg/ml; P â =â 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2â ±â 1.7 vs. 3.8â ±â 2.0; P â =â 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8â ±â 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1â ±â 165.6 ng/ml and 260.0â ±â 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8â ±â 285.6 vs. 433.0â ±â 227.2 ng/ml; P â =â 0.042). CONCLUSION: The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.
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Anticonvulsivantes , Citocromo P-450 CYP3A , Epilepsia , Nitrilas , Piridonas , Humanos , Citocromo P-450 CYP3A/genética , Criança , Feminino , Masculino , Epilepsia/tratamento farmacológico , Epilepsia/genética , Nitrilas/farmacocinética , Piridonas/farmacocinética , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Pré-Escolar , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Polimorfismo de Nucleotídeo Único/genética , Genótipo , Adolescente , Povo Asiático/genética , População do Leste AsiáticoRESUMO
BACKGROUND: Information on the efficacy and plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy is limited. Therefore, this real-world retrospective study aimed to assess the efficacy, tolerability, and plasma concentration of the maximum dose of PER for epilepsy treatment in Chinese pediatric patients. METHODS: A total of 107 pediatric patients from 2 hospitals in China were enrolled in this study. The plasma concentration of PER was determined using ultrahigh-performance liquid chromatography. The primary efficacy endpoint was the seizure reduction rate after PER treatment at the last follow-up. RESULTS: The response rate to PER therapy was 59.8% (64/107). The authors observed that patients younger than 6 years of age (n = 49) showed a significantly lower concentration-to-dose ratio than patients with ages between 6 and 14 years (n = 58) (2.2 ± 1.7 vs. 3.0 ± 1.8 mcg·mL -1 ·kg·mg -1 , respectively; P < 0.05). Patients who received enzyme-inducing antiseizure medication had significantly lower concentration-to-dose ratios than those who did not receive enzyme-inducing antiseizure medication (EIASM) (2.1 ± 1.8 vs. 3.1 ± 2.0 mcg·mL -1 ·kg·mg -1 , P < 0.05). A total of 37 patients (34.6%) reported treatment adverse events. Patients with somnolence and irritability had a significantly higher PER plasma concentration than the "no treatment-emergent adverse effect" groups ( P < 0.05). CONCLUSIONS: PER is an effective and well-tolerated treatment option for patients with epilepsy. To ensure the clinical efficacy and safety of PER in pediatric patients, it is necessary to monitor its plasma concentrations.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Epilepsia , Humanos , Criança , Adolescente , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Epilepsia/tratamento farmacológico , Nitrilas , Piridonas/efeitos adversos , Resultado do Tratamento , Quimioterapia CombinadaRESUMO
Purpose: The safety and effectiveness of perampanel in clinical settings involving Chinese pediatric patients are limited, as perampanel has only recently been approved for use in China, in September 2019. We aimed to evaluate the efficacy and tolerability of perampanel as an adjunctive therapy for pediatric patients with epilepsy aged ≥ 4 years in Xinjiang, Northwest China. Methods: Efficacy was assessed by measuring changes in seizure frequency at 3-, 6-, and 12-month follow-up compared with baseline. The baseline was 3 months before the addition of perampanel, and the seizure frequency was based on the patients' seizure diary. The safety and tolerability depended on the type and frequency of any adverse event during epilepsy treatment across all pediatric patients. Results: Overall, 67 pediatric patients from 2 different hospitals were enrolled in the study. Among the pediatric patients with seizures during the baseline period, the effective rates for all seizure types at 3, 6, and 12 months were 59.1%, 58.7%, and 57.4%, respectively. During perampanel treatment, 34 patients (50.7%) experienced at least 1 adverse reaction. Conclusion: Overall, this real-world retrospective study of pediatric patients validated that perampanel is an effective treatment option as an adjunctive therapy among pediatric patients with epilepsy aged ≥4 years.
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Anticonvulsivantes , Epilepsia , Humanos , Criança , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Piridonas/efeitos adversos , Resultado do Tratamento , Quimioterapia CombinadaRESUMO
OBJECTIVE: P-glycoprotein plays a role in drug resistance of epileptic patients by limiting gastrointestinal absorption and brain access to antiseizure medications. This study aimed to evaluate the association between ABCB1 polymorphisms and drug resistance in epileptic pediatric patients. METHODS: Three hundred seventy-seven epileptic pediatric patients were treated with antiseizure medications and subsequently divided into the drug-responsive group (n = 256, 68%) and drug-resistant group (n = 121, 32%). The genomic DNA of patients in the different groups was extracted, followed by the determination of the ABCB1 gene polymorphisms using polymerase chain reaction-fluorescence staining in situ hybridization. RESULTS: Drug-resistant patients significantly exhibited a combined generalized and focal onset than drug-responsive patients (χ2 = 12.278, P < 0.001). The TT (χ2 = 5.776, P = 0.016) genotypes of G2677T and CT (χ2 = 6.165, P = 0.013) and TT (χ2 = 11.121, P = 0.001) genotypes of C3435T were significantly more frequent in drug-resistant patients than drug-responsive patients. Similarly, the GT-CT diplotype was significantly more frequent in drug-resistant patients than in drug-responsive patients. CONCLUSION: Our study findings suggest that the ABCB1 G2677T and C3435T polymorphisms are significantly associated with drug resistance in epileptic patients.
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PURPOSE: The effectiveness and tolerability of lacosamide (LCM) among Chinese children and adolescents with refractory epilepsy has not yet been established. Therefore, the objective of this study was to assess the effectiveness and tolerability of LCM among children and adolescents with refractory epilepsy in Xinjiang, Northwest China. METHODS: Effectiveness was assessed by measuring changes in seizure frequency at 3, 6 and 12 months compared with baseline. Patients that achieved ≥ 50% reduction in the frequency of all seizures per month, relative to baseline, were considered to be responders. RESULTS: 105 children and adolescents with refractory epilepsy were enrolled in the study. The responder rates were 47.6%, 39.2%, and 31.9%, respectively at 3, 6, and 12 months. Seizure freedom rates were 32.4%, 28.9%, and 23.6% at 3, 6, and 12 months, respectively. The retention rates at 3, 6, and 12 months were 92.4%, 78.1%, and 69.5%, respectively. The maintenance dose of LCM within the responder group (8.2 ± 4.5 mg·kg- 1·d- 1) was significantly higher compared to the non-responder group (7.3 ± 2.3 mg·kg- 1·d- 1) (p < 0.05). At first follow-up, 44 patients (41.9%) reported experiencing at least one treatment-emergent adverse events. CONCLUSION: This real-world study of children and adolescents validated that LCM was both an effective and well-tolerated treatment option for the treatment of refractory epilepsy.
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Anticonvulsivantes , Epilepsia Resistente a Medicamentos , Humanos , Criança , Adolescente , Lacosamida/uso terapêutico , Anticonvulsivantes/efeitos adversos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Acetamidas/efeitos adversos , Resultado do Tratamento , Convulsões/tratamento farmacológico , Quimioterapia CombinadaRESUMO
BACKGROUND: The efficacy and safety of lacosamide (LCM) monotherapy in Chinese pediatric patients with epilepsy have not been established. Therefore, this real-world retrospective study aimed to assess the efficacy of 12 months after achievement the maximal dose and tolerability of LCM as monotherapy for epilepsy treatment in pediatric patients. METHODS: Pediatric patients were administered LCM monotherapy in two ways: primary or conversion monotherapy. Seizure frequency was recorded as an average per month for the preceding three months at baseline and then at each follow-up period for three, six, and 12 months. RESULTS: Primary monotherapy with LCM was administered to 37 (33.0%) pediatric patients, whereas conversion to monotherapy was achieved in 75 (67.0%) pediatric patients. The responder rates of pediatric patients receiving primary monotherapy with LCM at three, six, and 12 months were 75.7% (28 of 37), 67.6% (23 of 34), and 58.6% (17 of 29), respectively. The responder rates of pediatric patients receiving conversion to monotherapy with LCM at three, six, and 12 months were 80.0% (60 of 75), 74.3% (55 of 74), and 68.1% (49 of 72), respectively. The incidence of adverse reactions with conversion to LCM monotherapy and primary monotherapy was 32.0% (24 of 75) and 40.5% (15 of 37), respectively. CONCLUSION: LCM is an effective and well-tolerated treatment option as monotherapy for the treatment of epilepsy.
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Anticonvulsivantes , Epilepsia , Humanos , Criança , Lacosamida/efeitos adversos , Anticonvulsivantes/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/tratamento farmacológicoRESUMO
Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.
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Antifúngicos , Citocromo P-450 CYP3A , Humanos , Voriconazol/uso terapêutico , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP2C19/genética , Polimorfismo Genético/genética , Genótipo , Proteína 2 Associada à Farmacorresistência MúltiplaRESUMO
BACKGROUND AND OBJECTIVE: The impact of individual patient variables on drug metabolism is particularly important for antiseizure medication, and lacosamide has not been studied in Chinese pediatric patients with epilepsy. This study evaluated the effects of dose, age, sex, medication time, seizure type, and concomitant enzyme-inducing antiseizure medications (EIASMs) on the plasma concentration of lacosamide. METHODS: A total of 500 pediatric patients from two hospitals in China were enrolled in this study. Lacosamide plasma concentration was processed using an ultra-performance liquid chromatography assay. Efficacy was evaluated based on the four-grade therapeutic effect criteria developed by the first National Epilepsy Academic Conference of the Chinese Medical Association. RESULTS: The responder rate to lacosamide therapy was 72.2% (361/500). There was a weaker relationship between the lacosamide daily dose and lacosamide plasma concentration (r = 0.238). Lacosamide plasma concentrations of patients ranged from 1.5 to 19.7 µg/mL, with a mean of 6.9 ± 3.2 µg/mL. The study results showed a significant contribution of age, body mass index, epilepsy duration, medication time, and EIASMs to the lacosamide plasma concentration (p < 0.05). Patients taking concomitant EIASMs with lacosamide had a significantly lower mean lacosamide plasma concentration (5.9 ± 2.6 µg/mL) than patients taking concomitant non-EIASMs (7.5 ± 3.5 µg/mL, p < 0.001). CONCLUSION: To ensure the clinical efficacy and safety of lacosamide therapy in pediatric patients, it is necessary to monitor the plasma concentration.
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Anticonvulsivantes , Epilepsia , Humanos , Criança , Lacosamida , Anticonvulsivantes/efeitos adversos , Monitoramento de Medicamentos , Acetamidas/uso terapêutico , Epilepsia/tratamento farmacológicoRESUMO
PURPOSE: We aimed to evaluate the effect of the ABCC2 1249G>A (rs2273697) and -24C>T (rs717620) polymorphisms on lacosamide (LCM) plasma concentrations and the efficacy of LCM in Uygur pediatric patients with epilepsy. METHODS: We analyzed 231 pediatric patients with epilepsy, among which 166 were considered to be LCM responsive. For drug assays, 2-3 mL of venous blood was collected from each patient just before the morning LCM dose was administered (approximately 12 hours after the evening dose, steady-state LCM concentrations). The remaining samples after routine therapeutic drug monitoring were used for genotyping analysis. The χ 2 test and Fisher exact test were utilized for comparative analysis of the allelic and genotypic distribution of ABCC2 polymorphisms between the LCM-resistant and LCM-responsive groups. The Student t test or Mann-Whitney U test was conducted to analyze differences in plasma LCM concentration among pediatric patients with epilepsy with different genotypes. RESULTS: Patients with the ABCC2 1249G>A GA genotype (0.7 ± 0.3 mcg/mL per kg/mg) and AA genotype (0.5 ± 0.3 mcg/mL per kg/mg) showed significantly ( P < 0.001) lower LCM concentration-to-dose (CD) ratios than patients with the GG genotype (1.0 ± 0.4 mcg/mL per kg/mg). Moreover, patients with the ABCC2 -24C>T CT genotype (0.6 ± 0.2 mcg/mL per kg/mg) and TT genotype (0.6 ± 0.3 mcg/mL per kg/mg) presented a significantly ( P < 0.001) lower LCM CD ratio than patients with the CC genotype (1.1 ± 0.4 mcg/mL per kg/mg). CONCLUSIONS: The ABCC2 1249G>A (rs2273697) and ABCC2 -24C>T (rs717620) polymorphisms can affect plasma LCM concentrations and treatment efficacy among a population of Uygur pediatric patients with epilepsy, causing these patients to become resistant to LCM. In clinical practice, ABCC2 polymorphisms should be identified before LCM treatment, and then, the dosage should be adjusted for pediatric patients with epilepsy accordingly.
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Epilepsia , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Humanos , Criança , Lacosamida/uso terapêutico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Epilepsia/tratamento farmacológico , Epilepsia/genética , Proteína 2 Associada à Farmacorresistência Múltipla , Genótipo , Anticonvulsivantes/uso terapêuticoRESUMO
This study has developed and validated a novel LC-MS/MS assay method to quantify perampanel in pediatric patients with epilepsy in Xinjiang, China. Our assay reduces current specimen volume requirements and decreases the turnaround time for results. Samples were separated by gradient elution and then injected into the mass spectrometer with a total run time of 3 min per sample. The ions from the analytes were detected using multiple reactions by monitoring transitions of m/z 350.2-219.0 for perampanel and m/z 359.1-323.1 for the internal standard, as precursor ion and product ion, respectively. The peak area ratios of perampanel with internal standard within the plasma samples were linear in the concentration range of 0.1-3.2 µg/mL (y = 2.87x + 0.61; r2 ≥ 0.99). The within-run and between-run precision coefficient of variation (%) did not exceed 11.03%, and the accuracy (bias) ranged from -1.07 to 6.69%. The mean absolute recoveries of perampanel for four QC levels (lower limit of quantification, low quality control, middle quality control, and high quality control) determined by this method were 87.69, 94.04, 107.50, and 95.15%, respectively. The stability results for this method showed that the plasma samples of perampanel were stable under all tested conditions (86.43-104.81%), with a coefficient of variation (%) maximum of 8.74%.
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Epilepsia , Espectrometria de Massas em Tandem , Criança , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Epilepsia/tratamento farmacológico , Humanos , Nitrilas , Piridonas , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
BACKGROUND: P-glycoprotein, encoded by ABCB1 (or MDR1), may contribute to drug resistance in epilepsy by limiting gastrointestinal absorption and brain access to antiseizure medications. The study aimed to evaluate the impact of ABCB1 polymorphisms on lacosamide (LCM) serum concentrations in Uygur pediatric patients with epilepsy. METHODS: The serum concentrations of LCM were determined by ultrahigh performance liquid chromatography, and the ABCB1 polymorphism was analyzed through polymerase chain reaction-fluorescence staining in situ hybridization. The χ2 test and the Fisher exact test were used to analyze the allelic and genotypic distributions of ABCB1 polymorphisms between the drug-resistant and drug-responsive patient groups. Differences in steady-state and dose-corrected LCM serum concentrations between different genotypes were analyzed using the one-way analysis of variance and the Mann-Whitney test. RESULTS: A total of 131 Uygur children with epilepsy were analyzed, and of them, 41 demonstrated drug resistance. The frequency of the GT genotype of ABCB1 G2677T/A was significantly higher in the drug-resistant group than that in the drug-responsive group (P < 0.05, OR = 1.966, 95% CI, 1.060-3.647). Patients with the G2677T/A-AT genotype had a statistically significantly lower concentration-to-dose (CD) value than patients with the G2677T/A-GG genotype (mean: 0.6 ± 0.2 versus 0.8 ± 0.5 mcg/mL per mg/kg, P < 0.001). Significantly lower LCM serum concentrations were observed in ABCB1 C3435T CT and TT genotype carriers than those in the CC carriers (P = 0.008 and P = 0.002), and a significantly lower LCM CD value was observed in ABCB1 C3435T CT genotype carriers than that in the CC carriers (P = 0.042). CONCLUSIONS: ABCB1 G2677T/A and C3435T polymorphisms may affect LCM serum concentrations and treatment efficacy in Uygur pediatric patients with epilepsy, leading to drug resistance in pediatric patients.
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Epilepsia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Criança , Epilepsia/tratamento farmacológico , Epilepsia/genética , Frequência do Gene , Genótipo , Haplótipos , Humanos , Lacosamida/uso terapêutico , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
PURPOSE: Levetiracetam is approved as an add-on therapy to treat refractory partial seizures in pediatric patients over four years old. The efficacy and safety in pediatric patients with epilepsy in Uygur, China, is unknown. Therefore, the objective of this study was to investigate the safety, efficacy, and tolerability of levetiracetam in pediatric patients with epilepsy in Uygur, China. METHODS: This retrospective study compared the efficacy and safety of levetiracetam monotherapy and in combination with other antiseizure medications (ASMs) in 1055 pediatric patients with epilepsy treated with levetiracetam. The seizure frequencies at 1, 2, and 3â¯years after starting levetiracetam therapy were recorded and compared with the baseline yearly frequency. Safety variables included the incidence and type of adverse reactions. RESULTS: A total of 680 (64%) pediatric patients responded to levetiracetam therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, 13%, 15%, and 18% at 1, 2, and 3â¯years, respectively. The number of baseline ASMs and the order of levetiracetam introduction were highly significant, impacting the likelihood of seizure remission during a 3-year follow-up period (pâ¯<â¯0.001). During levetiracetam treatment, 233 pediatric patients (22%) experienced at least one adverse reaction. CONCLUSION: These significant findings indicate that levetiracetam is likely to become a widely prescribed ASM for epilepsy in pediatric clinical practice because of its long-term safety, efficacy, and tolerability.
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Epilepsia , Piracetam , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , China , Epilepsia/tratamento farmacológico , Humanos , Levetiracetam/uso terapêutico , Piracetam/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Lacosamide (LCM) was approved in China in 2018. However, the safety of LCM has not been established in pediatric patients. Therefore, the objective of this study was to investigate its safety, efficacy, and tolerability in pediatric patients living in Uygur, Northwest China. METHODS: This is a retrospective analysis of pediatric patients diagnosed with epilepsy and on LCM therapy at a medical center. The seizure frequencies at 3, 6, and 12â¯months after starting LCM therapy were recorded and compared with the baseline monthly frequency. The primary outcome variables were the 50% responder and seizure-free rates. The secondary outcome variables included the terminal 6-month seizure remission and percentages of discontinuation due to a lack of efficacy and tolerability. Safety variables included the incidence and type of adverse reactions. RESULTS: Seventy-two pediatric patients with epilepsy living in Uygur, China and receiving LCM treatment were included in the present study. Fifty (69%) children responded to LCM therapy with a more than 50% reduction in the frequency of seizures. Seizure-free rates increased over time, at 14%, 19%, and 20% at 3, 6, and 12 months, respectively. The number of baseline anti-seizure medications (ASMs) and order of LCM introduction significantly impacted the likelihood of seizure remission during the 12-month follow-up period (pâ¯<â¯0.05). During the entire period of LCM treatment, twenty-two children (30.5%) experienced at least one adverse reaction. CONCLUSION: This retrospective study of 72 pediatric patients with epilepsy in Uygur, China, showed that LCM therapy is safe and effective for epilepsy in children, resulting in a reduction in the seizure rate.
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Epilepsias Parciais , Epilepsia , Anticonvulsivantes/uso terapêutico , Criança , China , Epilepsias Parciais/tratamento farmacológico , Epilepsia/tratamento farmacológico , Humanos , Lacosamida/uso terapêutico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This study has developed and validated a novel UPLC method to quantify lacosamide (LCM), oxcarbazepine (OXC), and lamotrigine (LTG) in children with epilepsy in Xinjiang, China. Phenytoin sodium was used as the internal standard. The mobile phase contained ammonium dihydrogen phosphate solution (10 mmol/L, pH = 4.0) and methanol (55:45, v/v). The flow rate, injection volume, column temperature, and detection wavelength were 0.2 mL/min, 2 µL, 30°C, and 240 nm, respectively. The method was linear within 0.5-40, 2.5-80, and 2.5-40 µg/mL for LCM, 10-hydroxycarbazepine (MHD), and LTG, respectively (r2 ≥ 0.998). The intra- and inter-day precision as measured by the relative standard deviation values was between 1.36 and 4.50, 0.54 and 1.91, and 0.58 and 1.56%. Recovery ranged from 96.58 to 106.22%. All serum samples could be maintained for up to 3 h at ambient temperature, 24 h at 4°C, 30 days at -30°C, and after successive freeze-thaw cycles (24 h per cycle) in the absence of significant degradation.
Assuntos
Anticonvulsivantes/sangue , Cromatografia Líquida de Alta Pressão/métodos , Lacosamida/sangue , Lamotrigina/sangue , Oxcarbazepina/sangue , Adolescente , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , China , Epilepsia/tratamento farmacológico , Humanos , Lactente , Lacosamida/uso terapêutico , Lamotrigina/uso terapêutico , Limite de Detecção , Modelos Lineares , Oxcarbazepina/uso terapêutico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Interindividual variations in the efficacy of antiseizure medications make epilepsy treatment challenging. This is due to genetic factors such as gene polymorphisms in Adenosine-triphosphate (ATP)-binding cassette sub-family B member 1 (ABCB1). In this article, the impact of polymorphisms in the P-glycoprotein-encoding gene, ABCB1 (C1236T, G2677T/A, and C3435T), on levetiracetam disposition was evaluated in Uygur Chinese children with epilepsy. METHODS: MDR1 C3435T polymorphism was analyzed by polymerase chain reaction-fluorescence staining in situ hybridization. The χ test and Fisher exact test were used to analyze the allelic and genotypic distribution of ABCB1, C1236T, G2677T, and C3435T between the drug-resistant and drug-responsive groups. Differences in steady-state and dose-corrected levetiracetam serum concentrations between the different genotypes were analyzed using 1-way analysis of variance and Mann-Whitney test. RESULTS: Total 245 Uygur children with epilepsy were analyzed [drug-resistant, n = 117 (males:females = 53:64) and drug-responsive, n = 128 (males:females = 76:52)]. The frequency of ABCB1 C1236T, G2677T/A, and ABCB1 C3435T genotypes, alleles, haplotypes, or diplotypes did not differ significantly between the 2 groups (P > 0.05). Significantly higher levetiracetam concentrations and serum concentration/body mass dose were seen in ABCB1 2677-GT, TT, GA, and AT genotypes and 3435-TT carriers compared with GG and CC carriers (P = 0.021 and P = 0.002 versus P = 0.001 and P = 0.000, respectively). CONCLUSIONS: ABCB1 G2677T/A and C3435T may affect levetiracetam disposition and therapeutic efficacy in Uygur children with epilepsy. Genetic analysis could be a valuable tool for predicting the response to antiseizure medications before the start of treatment and could contribute to personalized medicine for Uygur children with epilepsy.
Assuntos
Anticonvulsivantes/sangue , Epilepsia/tratamento farmacológico , Levetiracetam/sangue , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , China , Epilepsia/etnologia , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Levetiracetam/uso terapêutico , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: To determine genetic associations between oxcarbazepine (OXC)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in the Uighur Chinese population. METHODS: A total of 208 patients were enrolled in this study, including 20 subjects with OXC-induced MPE (case group) and 188 OXC-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 208 Uighur patients using next-generation sequencing (NGS). RESULTS: The carried rate of HLA-A*03:01 was significantly different between the OXC-induced MPE group and the tolerant group (7/20, 35% versus 4/188, 2.13%; P = 0.000, odds ratio [OR] = 24.77, 95% confidence interval [CI] = 6.41-95.65). Additionally, the carried rate of HLA-B*07:02 was significantly different between the OXC-induced MPE group and the tolerant group (3/20, 15% versus 2/188, 0.011%; P = 0.000, odds ratio [OR] = 16.41, 95% confidence interval (CI) = 2.56-105.09). CONCLUSIONS: HLA-A*03:01 and HLA-B*07:02 may be the risk alleles for MPE in the Uighur Chinese population.
Assuntos
Anticonvulsivantes , Carbamazepina , Alelos , Anticonvulsivantes/efeitos adversos , Povo Asiático/genética , Carbamazepina/efeitos adversos , China , Predisposição Genética para Doença , Genótipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígeno HLA-B7 , Humanos , OxcarbazepinaRESUMO
PURPOSE: To determine genetic associations between antiseizure medications (ASMs)-induced maculopapular eruption (MPE) and human leukocyte antigen (HLA) variants in Xinjiang, China. METHODS: A total of 409 patients were enrolled in this study, including 36 subjects with ASMs-induced MPE (case group) and 373 ASMs-tolerant patients (control group). We detected the whole sequence of the HLA alleles in the 409 Uighur patients using next-generation sequencing (NGS). The carried rate of HLA alleles were compared between the case group, the control group, and the general Chinese population. RESULTS: The carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with both the ASMs-tolerant group (p = 0.000, odds ratio (OR) = 23.92, 95 % confidence interval (CI) = 3.96-74.84; p = 0.000, OR = 21.40, 95 % CI = 3.55-67.52; p = 0.030, OR = 4.69, 95 % CI = 0.90-61.73 and p = 0.000, OR = 18.94, 95 % CI = 3.15-60.58; respectively), and the general Chinese population (p = 0.000, OR = 21.34, 95 % CI = 3.31-38.98; p = 0.000, OR = 23.92, 95 % CI = 3.96-74.84; p = 0.019, OR = 5.53, 95 % CI = 0.14-19.86 and p = 0.000, OR = 21.67, 95 % CI = 3.68-11.73; respectively). Moreover, the carried rate of the HLA-B*4001 allele was significantly higher in the ASMs-tolerant group when compared with the ASMs-MPE group (p = 0.024, OR = 5.13, 95 % CI = 1.01-9.99). CONCLUSIONS: In this study, we identified for the first time that the carried rate of HLA-A*03:01, HLA-B*07:02, HLA-C*01:02, and HLA-DRB1 *06:09 allele was significantly higher in the ASMs-MPE group when compared with the ASMs-tolerant group.