■倍他司汀于1970年代在欧洲注册,并在80多个国家/地区被批准作为梅尼埃病的一线治疗方法。它已被用于超过1.5亿患者。然而,根据Cochrane对倍他司汀的系统评价和最近的荟萃分析,没有足够的证据表明倍他司汀在目前批准的剂量高达48mg/d时是否有任何作用。与单胺氧化酶B(MAO-B)抑制剂的组合,司来吉兰,可将倍他司汀的生物利用度提高到与L-DOPA与卡比多巴或苄丝肼联合治疗帕金森病相似的水平。我们研究了司来吉兰对倍他司汀药代动力学的影响以及该组合在人体中的安全性。
■在研究者发起的前瞻性中,非随机化,单序列,两周期滴定,开放标签单中心第一阶段研究,15名健康志愿者接受三次单次口服倍他司汀(24、48和96毫克,至少2天的洗脱期),不使用和使用司来吉兰(5毫克/天,7天的负荷期)。在8个时间点的240分钟内测量倍他司汀血清浓度(曲线下面积,AUC0-240分钟)。该试验已在EudraCT(2019-002610-39)和ClinicalTrials.gov注册。
■在所有三种单一倍他司汀剂量中,司来吉兰可使倍他司汀的生物利用度增加约80至100倍。例如,单独使用倍他司汀48mg的曲线下面积平均值(±SD)为0.64(+/-0.47)h*ng/mL,而倍他司汀加司来吉兰的曲线下面积平均值(±SD)为53.28(+/-37.49)h*ng/mL.大约30分钟的半衰期基本上不受影响,除了24毫克倍他司汀的剂量。总的来说,记录了14次轻度不良事件。
■这项1期试验表明,MAO-B抑制剂司来吉兰使倍他司汀的生物利用度提高了约80至100倍。未检测到安全问题。增加的生物利用度是否对梅尼埃病的预防性治疗有影响,急性前庭综合征,或BPPV后残留的头晕必须在安慰剂对照试验中进行评估。
■https://clinicaltrials.gov/study/NCT05938517?intr=倍他司汀%20和%20selegiline&rank=1,标识符:NCT05938517。
UNASSIGNED: Betahistine was registered in Europe in the 1970s and approved in more than 80 countries as a first-line treatment for Menière\'s disease. It has been administered to more than 150 million patients. However, according to a Cochrane systematic review of betahistine and recent meta-analyses, there is insufficient evidence to say whether betahistine has any effect in the currently approved dosages of up to 48 mg/d. A combination with the monoamine oxidase B (MAO-B) inhibitor, selegiline, may increase the bioavailability of betahistine to levels similar to the well-established combination of L-DOPA with carbidopa or benserazide in the treatment of Parkinson\'s disease. We investigated the effect of selegiline on betahistine pharmacokinetics and the safety of the combination in humans.
UNASSIGNED: In an investigator-initiated prospective, non-randomized, single-sequence, two-period titration, open label single-center phase 1 study, 15 healthy volunteers received three single oral dosages of betahistine (24, 48, and 96 mg in this sequence with at least 2 days\' washout period) without and with selegiline (5 mg/d with a loading period of 7 days). Betahistine serum concentrations were measured over a period of 240 min at eight time points (area under the curve, AUC0-240 min). This trial is registered with EudraCT (2019-002610-39) and ClinicalTrials.gov.
UNASSIGNED: In all three single betahistine dosages, selegiline increased the betahistine bioavailability about 80- to 100-fold. For instance, the mean (±SD) of the area under curve for betahistine 48 mg alone was 0.64 (+/-0.47) h*ng/mL and for betahistine plus selegiline 53.28 (+/-37.49) h*ng/mL. The half-life time of around 30 min was largely unaffected, except for the 24 mg betahistine dosage. In total, 14 mild adverse events were documented.
UNASSIGNED: This phase 1 trial shows that the MAO-B inhibitor selegiline increases betahistine bioavailability by a factor of about 80 to 100. No safety concerns were detected. Whether the increased bioavailability has an impact on the preventive treatment of Menière\'s disease, acute vestibular syndrome, or post-BPPV residual dizziness has to be evaluated in placebo-controlled trials.
UNASSIGNED: https://clinicaltrials.gov/study/NCT05938517?intr=betahistine%20and%20selegiline&rank=1, identifier: NCT05938517.