Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- area under the curve (AUC0-∞)
研究概览
简要总结
The primary objective of the study is:
•To describe extent and rate of absorption of methantheline after single oral dose administration of Vagantin® coated tablets (Test) in comparison to a methantheline bromide solution (Reference)
The secondary objectives of the study are:
- To determine elimination the half-life of methantheline bromide
- To describe the effects of Test and Reference on salivation, accommodation, pupil response, blood pressure and heart rate
- to assess frequency and intensity of adverse drug reactions
详细描述
The quarternary anticholinergic compound methantheline bromide (diethyl-methyl [2-(9 xanthenyl carbonyloxy) ethyl] ammonium bromide) is marketed to treat neurogenic bladder instability. In comparison with atropine, it influences the parasympathetic nervous transmission more by ganglionic rather than peripheral muscarinic receptor blockade. Clinical effects after single therapeutic doses of 50-100 mg last for about 6 hours which is longer than after atropine. The drug relaxes smooth muscles of the gastrointestinal and urogenital tract. Furthermore, it inhibits bronchial, salivary and sweat glands secretion, lowers the production of gastric juice and disturbs accommodation.
There are no data available on the pharmacokinetic properties of methantheline in man. However, 25-50 mg intravenous methantheline seem to be equivalent to 50-100 mg p.o. with regard to the pharmacodynamic effects [Stille 1988].
Vagantin® is marketed as coated tablets containing 50 mg methantheline bromide. Because of the particular properties of methantheline (narrow therapeutic range, obviously erratic, incomplete and irregular absorption) and because of the national and international recommendations concerning the registration of drugs, Vagantin® must be evaluated with regard to its pharmacokinetic properties at least relative to a non-formulated form.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age: 18 - 45 years
- •sex: male and female
- •ethnic origin: Caucasian
- •body weight: ±20 % of normal weight (Broca)
- •good health as evidenced by the results of the clinical examination and the laboratory check-up which are judged by the clinical investigator not to differ in a clinical relevant way from the normal state
- •written informed consent
排除标准
- •known hypersensitivity to the investigational products or to their adjuvants
- •pollakisurie of cardial and renal reasons
- •megacolon
- •atonia of the gastrointestinal tract
- •atonia or hypotonia of the urinary bladder
- •tachycardiac arrhythmia
- •subvesical bladder obstruction, especially benign prostatic hypertrophy
- •narrow angle glaucoma
- •glasses or contact lenses
- •history of gastrointestinal diseases (except appendectomy)
- •history of renal and/or hepatic diseases
- •any disease known to modify absorption, metabolism or excretion of the drug under investigation
- •liability to orthostatic dysregulation, faintings, or blackouts
- •alcohol consumption more than 40 g/day
- •smokers of more than 10 cigarettes per day
- •special or uniform nutritional habits, e.g. vegetarians or under-caloric diet
- •less than 14 days after last acute disease
- •less than 14 days after last systemic or local drug administration or 10 times the half life of the respective drug (except hormonal contraceptives)
- •blood donation within the last two months
- •blocking period due to another clinical study with investigational products; however at least 4 weeks after the end of the study or 10 times the half life of the respective drug
- •lack of willingness or inability to co-operate adequately
- •HIV and HBV and drug screening positive or not performed (in case of a positive HIV-test, the volunteers must be informed by a physician in a personal conversation)
- •lactation and pregnancy test positive or not performed
研究组 & 干预措施
Test
Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
干预措施: blood sampling (Procedure)
Test
Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
干预措施: Vagantin® (Drug)
Test
Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
干预措施: Measurement of salivation (Procedure)
Test
Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
干预措施: Measurement of accommodation (Procedure)
Test
Pharmacokinetics and -dynamics after single dose administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
干预措施: Pupillometry (Procedure)
Reference
Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)
干预措施: blood sampling (Procedure)
Reference
Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)
干预措施: methantheline solution (Drug)
Reference
Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)
干预措施: Measurement of salivation (Procedure)
Reference
Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)
干预措施: Measurement of accommodation (Procedure)
Reference
Pharmacokinetics and -dynamics after single dose administration 100 ml methantheline solution (100 mg methantheline bromide)
干预措施: Pupillometry (Procedure)
结局指标
主要结局
area under the curve (AUC0-∞)
时间窗: 0-16 h plasma concentration-time profile of methantheline after single oral administration
AUC0-∞ was assessed by the trapezoidal formula up to the last sampling time with a concentration above the limit of quantitation (AUC0-), and was extrapolated to infinity using standard techniques
maximal plasma concentration (Cmax)
时间窗: 0-16 h plasma concentration-time profile of methantheline after single oral administration
Cmax was obtained directly from the measured concentration-time curves
次要结局
- time of maximal plasma concentration (tmax)(0-16 h plasma concentration-time profile of methantheline after single oral administration)
- terminal half-life (t½)(0-16 h plasma concentration-time profile of methantheline after single oral administration)
- volume of salivary gland secretion(before and 0, 0.5, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication)
- Measurement of accommodation(before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication)
- Pupil function(before and 0, 1, 2, 3, 4, 6, 8, 12 hours after administration of study medication)