Tiotropium in Combination With Concomitant Cimetidine or Ranitidine in Healthy Male and Female Subjects

Inclusion criteria

• Healthy males or females
• Age range from 50 to 65 years
• Within 20% of their normal weight (Broca index)

Exclusion criteria

• Any finding of the medical examination (including blood pressure, puls rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or with psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of a drug with a long half-life (≥ 24 hours) within ten half-lives of the respective drug before enrolment in the study or during the study (exclusion: ovarian hormone substitution)
• Use of any drugs which might influence the results of the trial within four weeks prior to administration or during the trial, among these all non-selective β-blockers, cromolyn sodium, nedocromil sodium, oral β-adrenergics or long-acting β-adrenergics such as salmeterol and formoterol, and anticholinergic drugs including ATROVENT® (ipratropium) by oral inhalation or ATROVENT® Nasal Spray
• Participation in another study with an investigational drug within two months prior to administration or during the trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day)
• Inability to refrain from smoking on study days
• Alcohol abuse (> 40 g/day)
• Drug abuse
• Blood donation (≥ 100 ml) within four weeks prior to administration or during the trial
• Excessive physical activities within 5 days prior to administration or during the trial
• Any laboratory value outside the reference range of clinical relevance
• Subjects with known hypersensitivity to anticholinergic drugs
• Subjects with known symptomatic prostatic hypertrophy or disturbed micturition
• Subjects with known narrow-angle glaucoma

In addition for female subjects (if appropriate):

• Pregnancy
• Positive pregnancy test
• No adequate contraception e.g. oral contraceptives, sterilization, intra uterine pessary (IUP)
• Inability to maintain this adequate contraception during the whole study period
• Lactation period