Bioequivalence Study of Two Tablet Formulations of Clonazepam 2 mg: A Randomized, Open-Label, Crossover Study in Healthy Mexican Volunteers Under Fasting Conditions.
IF 3.9
3区 医学
Q1 CLINICAL NEUROLOGY
引用次数: 0
Abstract
Introduction: The prevalence of neurological disorders is high among the Mexican population. Clonazepam is primarily indicated to treat panic disorders, certain kinds of epilepsy such as status epilepticus, childhood motor seizures (petit mal absence, Lennox-Gastaut syndrome, and infantile spasms), anxiety, and muscle spasm. This study was performed to compare bioequivalence between two oral tablet formulations of clonazepam 2 mg in healthy Mexican volunteers under fasting conditions.
Methods: This phase I, randomized, open-label, two-treatment, crossover study included 30 healthy volunteers. Subjects were randomly assigned to either test or reference formulation of clonazepam 2 mg. Each study period was separated by 21-day washout period. Blood samples were collected at pre-dose and up to 72 h after drug administration. Clonazepam concentrations were determined using a validated ultra-flow liquid chromatography-tandem mass spectrometric method. Pharmacokinetic parameters were determined using a non-compartmental method. Two formulations were considered bioequivalent if geometric mean ratios (test/reference) were between 80% and 125%. Safety was evaluated by recording adverse events.
Results: Pharmacokinetic parameters were comparable between test and reference formulations. The mean maximum plasma concentration (Cmax) was ≈ 13 ng/mL, area under the plasma concentration-time curve from time 0 to last measurable concentration (AUC0-t) was ≈ 360 ng h/mL, time to reach maximum plasma concentration (Tmax) was ≈ 3 h, and elimination half-life (t1/2) was ≈ 43 h. Geometric mean ratios (90% confidence interval) of Cmax (99.2-115.3%), AUC0-t (100.6-110.6%), and AUC0-∞ (98.5-111.6%) were within the bioequivalence range. Seven non-serious adverse events (mostly asymptomatic hypotension) were recorded.
Conclusion: The test and reference formulations of clonazepam 2 mg were bioequivalent and well tolerated in healthy Mexican volunteers under fasting conditions.
Protocol authorization number: 213301410B0051 (Approved on April 13, 2021).
两种氯硝西泮2mg片剂的生物等效性研究:一项随机、开放标签、交叉研究，在墨西哥健康志愿者禁食条件下进行。
简介:墨西哥人口中神经系统疾病的患病率很高。氯硝西泮主要用于治疗惊恐障碍、某些类型的癫痫，如癫痫持续状态、儿童运动癫痫发作(小症状缺失、lenox - gastaut综合征和婴儿痉挛)、焦虑和肌肉痉挛。本研究比较了两种口服氯硝西泮2毫克片剂在墨西哥健康志愿者空腹条件下的生物等效性。方法:该I期随机、开放标签、双治疗、交叉研究包括30名健康志愿者。受试者被随机分配到氯硝西泮2 mg的试验制剂或参比制剂。每个研究期都有21天的洗脱期。在给药前和给药后72小时采集血样。氯硝西泮的浓度采用超流液相色谱-串联质谱法测定。采用非室室法测定药代动力学参数。如果几何平均比率(试验/参比)在80%至125%之间，则认为两种制剂具有生物等效性。通过记录不良事件来评估安全性。结果:试验方与参比方的药动学参数具有可比性。平均最大血药浓度(Cmax)≈13 ng/mL，从时间0到最后可测浓度(AUC0-t)的血药浓度-时间曲线下面积(AUC0-t)≈360 ng h/mL，达到最大血药浓度(Tmax)的时间(Tmax)≈3 h，消除半衰期(t1/2)≈43 h。Cmax(99.2 ~ 115.3%)、AUC0-t(100.6 ~ 110.6%)和AUC0-∞(98.5 ~ 111.6%)的几何平均比值(90%置信区间)均在生物等效性范围内。记录了7个非严重不良事件(主要是无症状性低血压)。结论:氯硝西泮2 mg试验剂型与对照剂型具有生物等效性，在墨西哥健康志愿者空腹条件下耐受性良好。协议授权号:213301410B0051(2021年4月13日批准)。
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来源期刊
Neurology and Therapy
CLINICAL NEUROLOGY-
CiteScore
5.40
自引率
8.10%
发文量
103
审稿时长
6 weeks
期刊介绍：
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Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice.
Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
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