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Tiotropium
- indication:Used in the management of chronic obstructive pulmonary disease (COPD).
- pharmacologypharmacology:
- mechanism: Tiotropium is a muscarinic receptor antagonist, often referred to as an antimuscarinic or anticholinergic agent. Although it does not display selectivity for specific muscarinic receptors, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.
- toxicity: No mortality was observed at inhalation tiotropium doses up to 32.4 mg/kg in mice, 267.7 mg/kg in rats, and 0.6 mg/kg in dogs. These doses correspond to 7,300, 120,000, and 850 times the recommended human daily dose on a mg/m2 basis, respectively.
- absorprion: Bioavailability is 19.5% following administration by inhalation. Oral solutions of tiotropium have an absolute bioavailability of 2-3%.
- halflife: 5-6 days
- roouteelimination: Intravenously administered tiotropium was mainly excreted unchanged in urine (74%). After dry powder inhalation, urinary excretion was 14% of the dose, the remainder being mainly non-absorbed drug in the gut which was eliminated via the feces.
- volumedistribution: * 32 L/kg
- clearance: * 880 mL/min [young healthy volunteers receiving IV administration] * Renal cl=326 mL/min [COPD patients (<58 years)] * Renal cl=163 mL/min [COPD patients (>70 years)]