Glycopyrronium is hydrolyzed to the inactive M9 metabolite. Metabolism was mainly mediated by CYP2D6, with minor contributions from CYP1A2, CYP2B6, CYP2C9, CYP2C18, CYP2C19, and CYP3A4.
◉ Summary of Use during Lactation:No information is available on the use of glycopyrrolate during breastfeeding. Because glycopyrrolate is a quaternary ammonium compound, it is not likely to be absorbed and reach the bloodstream of the infant, especially when given by inhalation or topically on the skin. Long-term oral use of glycopyrrolate might reduce milk production or milk letdown, but a single dose is unlikely to interfere with breastfeeding. During long-term use, observe for signs of decreased lactation such as poor weight gain.
◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk:Relevant published information in nursing mothers was not found as of the revision date. Anticholinergics can inhibit lactation in animals, apparently by inhibiting growth hormone and oxytocin secretion. Anticholinergic drugs can also reduce serum prolactin in nonnursing women. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
来源:Drugs and Lactation Database (LactMed)
毒理性
蛋白质结合
Glycopyrronium is 38-44% protein bound in plasma. It is bound to serum albumin, alpha-1-acid glycoprotein, as well as other plasma proteins that have not been identified in literature.
吉库溴铵在血浆中与蛋白质的结合率为38-44%。它与血清白蛋白、α-1-酸性糖蛋白以及文献中尚未确定的其他血浆蛋白质结合。
Glycopyrronium is 38-44% protein bound in plasma. It is bound to serum albumin, alpha-1-acid glycoprotein, as well as other plasma proteins that have not been identified in literature.
In adults, a 66 mg topical dose of glycopyrronium reaches a Cmax of 0.08 ± 0.04 ng/mL, with a Tmax of 1 hour, and an AUC0-24 of 0.88 ± 0.57 h\*ng/mL. Inhaled glycopyrronium is approximately 40% bioavailable. A 25 µg inhaled solution reaches a Cmax of 34.5 pg/mL, with a Tmax of <20 minutes, and an AUC0-inf of 255 h\*pg/mL. An 8 µg/kg intramuscular dose reaches a Cmax of 3.47 ± 1.48 µg/L, with a Tmax of 27.48 ± 6.12 minutes, and an AUC of 6.64 ± 2.33 h\*g/L. Oral glycopyrronium has highly variable pharmacokinetics, reaching a mean Cmax of 0.318 ng/mL, a Tmax of 3.1 hours, and an AUC0-24 of 1.74 h\*ng/mL.
85% of an intravenous dose was recovered in the urine, with <5% recovered in the bile. >80% of the recovered dose is the unchanged parent drug. The remainder is recovered as the inactive M9 metabolite.
The mean volume of distribution in patients aged 1-14 years old is 1.3-1.8 L/kg, with a range of 0.7-3.9 L/kg. The volume of distribution in adults aged 60-75 years is 0.42 ± 0.22 L/kg.
A 6 µg/kg intravenous dose has a clearance of 0.54 ± 0.14 L/kg/h. An oral solution has a clearance of 5.28-38.95 L/h/kg in healthy adults and 8.07-25.65 L/h/kg in patients with cerebral palsy.
TREATMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE WITH NEBULIZED BETA 2-AGONIST OR COMBINED NEBULIZED BETA 2-AGONIST AND ANTICHOLINERGIC ADMINISTRATION
The present invention is directed to novel compounds of Formula (I) and pharmaceutically acceptable salts thereof,
pharmaceutical compositions and their use as dual chromaphores having inhibitory activity against PDE4 and muscarinic acetylcholine receptors (mAChRs), and thus being useful for treating respiratory diseases.
[EN] DUAL PHARMACOPHORES - PDE4-MUSCARINIC ANTAGONISTICS<br/>[FR] PHARMACOPHORES DUALS, ANTAGONISTES DES RÉCEPTEURS MUSCARINIQUES ET INHIBITEURS DE L'ACTIVITÉ PDE4
申请人：GLAXO GROUP LTD
公开号：WO2009100169A1
公开（公告）日：2009-08-13
The present invention is directed to novel compounds of Formula's (I) - (VI), and pharmaceutically acceptable salts thereof, pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of and/or prophylaxis of respiratory diseases, including inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
[EN] PYRROLOTRIAZINONE DERIVATIVES AS PI3K INHIBITORS<br/>[FR] DÉRIVÉS DE PYRROLOTRIAZINONE EN TANT QU'INHIBITEURS DES PI3K
申请人：ALMIRALL SA
公开号：WO2014060432A1
公开（公告）日：2014-04-24
New pyrrolotriazinone derivatives having the chemical structure of formula (I), are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Phosphoinositide 3-Kinases (PI3Ks)
Provided is a novel therapeutic agent for chronic obstructive pulmonary disease.
Provided are a quinuclidine derivative and a medicament comprising the quinuclidine derivative.
wherein R
1
represents a hydrogen atom, a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group; Y represents —C(C═O)—O—, —CH
2
—, or —CH
2
O—; m represents an integer of 1 to 5; Z represents an oxygen atom or a sulfur atom; l represents a number of 0 or 1; n represents an integer of 0 to 4; X
−
represents an anion; and a substituent of a quinuclidine ring represents a 1,3-bond, or 1,4-bond, provided that when m is 3, l is 1, and n is 0, R
1
represents a halogen atom, a lower alkyl group, a haloalkyl group, a lower alkoxy group, or a haloalkoxy group.
Disclosed are compounds of general formula (I),
wherein the groups A, R
1
, R
2
, R
a
and R
b
have the meanings given in the claims and specification, the tautomers, racemates, enantiomers, diastereomers and the mixtures thereof, and optionally the pharmacologically acceptable acid addition salts, solvates and hydrates thereof, and processes for preparing these thiazolyl-dihydro-quinazolines and the use thereof as pharmaceutical compositions.
