Tìm theo
Tiotropium
Thuốc tác dụng trên đường hô hấp
Thuốc Gốc
Small Molecule
CAS: 186691-13-4
ATC: R03BB04
ĐG : Boehringer Ingelheim Ltd. , http://www.boehringer-ingelheim.com
CTHH: C19H22NO4S2
PTK: 392.512
Tiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium is a muscarinic receptor antagonist, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H22NO4S2
Phân tử khối
392.512
Monoisotopic mass
392.099024577
InChI
InChI=1S/C19H22NO4S2/c1-20(2)12-9-11(10-13(20)17-16(12)24-17)23-18(21)19(22,14-5-3-7-25-14)15-6-4-8-26-15/h3-8,11-13,16-17,22H,9-10H2,1-2H3/q+1/t11?,12-,13+,16+,17-
InChI Key
InChIKey=LERNTVKEWCAPOY-KYQOMENCSA-N
IUPAC Name
(1R,2S,4R,5S)-7-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.0^{2,4}]nonan-9-ium
Traditional IUPAC Name
(1R,2S,4R,5S)-7-{[2-hydroxy-2,2-bis(thiophen-2-yl)acetyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.0^{2,4}]nonan-9-ium
SMILES
C[N+]1(C)[C@H]2CC(C[C@@H]1[C@@H]1O[C@H]21)OC(=O)C(O)(C1=CC=CS1)C1=CC=CS1
Độ hòa tan
1.56e-02 g/l
logP
-1.8
logS
-4.4
pKa (strongest acidic)
10.35
pKa (Strongest Basic)
-4.3
PSA
59.06 Å2
Refractivity
109.18 m3·mol-1
Polarizability
39.69 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
3
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
5
Bioavailability
1
Rule of Five
true
Dược Lực Học : Tiotropium is a long–acting, antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors, M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3–receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies prevention of methacholine–induced bronchoconstriction effects were dose–dependent and lasted longer than 24 hours. The bronchodilation following inhalation of tiotropium is predominantly a site–specific effect.
Cơ Chế Tác Dụng : Tiotropium is a long-acting, 24 hour, anticholinergic bronchodilator used in the management of chronic obstructive pulmonary disease (COPD). Tiotropium is a muscarinic receptor antagonist, on topical application it acts mainly on M3 muscarinic receptors located in the airways to produce smooth muscle relaxation, thus producing a bronchodilatory effect. 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.
Dược Động Học :
▧ Absorption :
Bioavailability is 19.5% following administration by inhalation. Oral solutions of tiotropium have an absolute bioavailability of 2-3%.
▧ Volume of Distribution :
* 32 L/kg
▧ Protein binding :
72% bound to plasma proteins.
▧ Metabolism :
The extent of biotransformation appears to be small. This is evident from a urinary excretion of 74% of unchanged substance after an intravenous dose to young healthy volunteers. Tiotropium, an ester, is nonenzymatically cleaved to the alcohol N–methylscopine and dithienylglycolic acid, neither of which bind to muscarinic receptors. In vitro experiments with human liver microsomes and human hepatocytes suggest that a fraction of the administered dose (74% of an intravenous dose is excreted unchanged in the urine, leaving 25% for metabolism) is metabolized by cytochrome P450–dependent oxidation and subsequent glutathione conjugation to a variety of Phase II metabolites. Via inhibition studies, it is evident that CYP450 2D6 and 3A4 are involved in the metabolic pathway that is responsible for the elimination of a small part of the administered dose.
▧ Route of Elimination :
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.
▧ Half Life :
5-6 days
▧ 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)]
Độc Tính : 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.
Chỉ Định : Used in the management of chronic obstructive pulmonary disease (COPD).
Tương Tác Thuốc :
  • Potassium Chloride The ulcerative effects of solid oral dosage forms of KCl may be enhanced by Tiotropium, an anticholinergic. Anticholinergics slow gastric emptying, increasing the contact time between the gastrointestinal mucosa and KCl. Prolonged exposure to KCl increases the risk of gastric and intestinal irritation and ulceration. Solid oral dosage forms of KCl should be avoided; alternatives include liquid or effervescent potassium preparations.
  • Pramlintide The anticholinergic effects of Tiotropium may be enhanced by Pramlintide. Additive effects of reduced GI motility may occur. Pramlintide slows gastic emptying and should not be used with drugs that alter GI motility (e.g. anticholinergics). Consider alternative treatments or use caution during concomitant therapy.
  • Secretin The stimulatory effect of Secretin may be reduced by anticholinergics such as Tiotropium. Concomitant use of Secretin and drugs with substantial anticholinergic effects should be avoided. If combination therapy must be used, Secretin efficacy should be closely monitored.
  • Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Tiotropium, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
  • Trimethobenzamide Trimethobenzamide and Tiotropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Triprolidine Triprolidine and Tiotropium, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
  • Trospium Trospium and Tiotropium, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Liều Lượng & Cách Dùng : Capsule - Respiratory (inhalation)
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Spiriva
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01409
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3086654
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504448
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0597-0075-75
PharmGKB
http://www.pharmgkb.org/drug/PA164769056
Wikipedia
http://en.wikipedia.org/wiki/Tiotropium
RxList
http://www.rxlist.com/cgi/generic/spiriva.htm
Drugs.com
http://www.drugs.com/cdi/tiotropium.html
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