Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
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
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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