Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution
Condition: Neurogenic Bladder
MeSH terms: Urinary Bladder, Neurogenic
Study type: Interventional
Phase: Phase 1

Summary: 
      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
    

Detailed description: 
      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.
    

Intervention name(s): blood sampling; Vagantin®; methantheline solution; Measurement of salivation; Measurement of accommodation; Pupillometry
Intervention type(s): Procedure; Drug; Drug; Procedure; Procedure; Procedure
Intervention description(s): blood sampling before and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16 hours after administration of study medication; administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide); administration 100 ml methantheline solution (100 mg methantheline bromide); Volume of salivary gland secretion was measured by chewing a 5 x 5 cm piece of PARAFILM "M"® (American Can Company, UK) for 5 min. Saliva was collected in glass tubes and the amount of the stimulated saliva was measured by weighing; Accommodation was measured with the optometer according to Schober (Velhagen 1972); Pupil function was assessed with the pupillograph (Compact Integrated Pupillograph, AMTech, Weinheim, Germany). The following data were obtained: pupil diameter, response to defined flash stimuli
Intervention MeSH terms: Methantheline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Pharmacokinetics; Accommodation, Ocular; Reflex, Pupillary; Salivation