NCT01429090

Bioavailability of Vagantin® Coated Tablets Relative to an Oral Methantheline Bromide Solution

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: University Medicine Greifswald · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Neurogenic Bladder

Interventions

Type	Name	Description
PROCEDURE	blood sampling	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
DRUG	Vagantin®	administration of 2 coated tablets Vagantin® (coated tablets of 50 mg methantheline bromide)
DRUG	methantheline solution	administration 100 ml methantheline solution (100 mg methantheline bromide)
PROCEDURE	Measurement of salivation	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
PROCEDURE	Measurement of accommodation	Accommodation was measured with the optometer according to Schober (Velhagen 1972)
PROCEDURE	Pupillometry	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

Timeline

• Start date: 1999-10-01
• Primary completion: 1999-11-01
• Completion: 2000-01-01
• First posted: 2011-09-05
• Last updated: 2011-09-05

Locations

1 site across 1 country: Germany