Pioglitazone is extensively metabolized by both hydroxylation and oxidation - the resulting metabolites are also partly converted to glucuronide or sulfate conjugates. The pharmacologically active M-IV and M-III metabolites are the main metabolites found in human serum and their circulating concentrations are equal to, or greater than, those of the parent drug. The specific CYP isoenzymes involved in the metabolism of pioglitazone are CYP2C8 and, to a lesser degree, CYP3A4. There is also some evidence to suggest a contribution by extrahepatic CYP1A1.
Isoforms of cytochrome P450 (CYP) are involved in the metabolism of pioglitazone, including CYP2C8 and, to a lesser degree, CYP3A4. CYP2C9 is not significantly involved in the elimination of pioglitazone. Pioglitazone is not a strong inducer of CYP3A4, and pioglitazone was not shown to induce CYPs.
Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates. Metabolites M-III (keto derivative of pioglitazone) and M-IV (hydroxyl derivative of pioglitazone) are the major circulating active metabolites in humans.
Pioglitazone has known human metabolites that include 2-[6-(2-{4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy}ethyl)pyridin-3-yl]acetic acid, 5-({4-[2-(5-ethylpyridin-2-yl)-2-hydroxyethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione, and 5-[(4-{2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy}phenyl)methyl]-1,3-thiazolidine-2,4-dione.
IDENTIFICATION AND USE: Pioglitazone is a solid. It is used as hypoglycemic agent as an adjunct to diet and exercise for the management of type 2 diabetes mellitus. HUMAN STUDIES: Pioglitazone hydrochloride is a thiazolidinedione that depends on the presence of insulin for its mechanism of action. Pioglitazone hydrochloride decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. Pioglitazone is an agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma). PPAR receptors are found in tissues important for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPARgamma nuclear receptors modulates the transcription of a number of insulin responsive genes involved in the control of glucose and lipid metabolism. No evidence of hepatotoxicity has been noted with pioglitazone in clinical studies to date. However, hepatitis, liver function test abnormalities (such as elevations in hepatic enzymes to at least 3 times the upper limit of normal), mixed hepatocellular-cholestatic liver injury, and liver failure with or without fatalities have been reported during postmarketing experience with the drug. Thiazolidinediones, including pioglitazone hydrochloride, cause or exacerbate congestive heart failure in some patients. Pioglitazone-induced heart failure is known in patients with underlying heart disease, but is not well documented in patients with normal left ventricular function. It has been however reported that a patient developed congestive heart failure and pulmonary edema with normal left ventricular function within 1 year of starting pioglitazone therapy. Patients treated with pioglitazone have increased risk of bladder cancer compared to general population. There was also described an association of pioglitazone use with an increased risk of newly developed chronic kidney disease. ANIMAL STUDIES: Heart enlargement was seen in a 13-week study in monkeys at oral doses of 8.9 mg/kg and above, but not in a 52-week study at oral doses up to 32 mg/kg. Heart enlargement has been observed in mice (100 mg/kg), rats (4 mg/kg and above) and dogs (3 mg/kg) treated orally with pioglitazone hydrochloride. In a one-year rat study, drug-related early death due to apparent heart dysfunction occurred at an oral dose of 160 mg/kg/day. A two-year carcinogenicity study was conducted in male and female rats at oral doses up to 63 mg/kg. Drug-induced tumors were not observed in any organ except for the urinary bladder. A two-year carcinogenicity study was conducted in male and female mice at oral doses up to 100 mg/kg/day. No drug-induced tumors were observed in any organ. No adverse effects upon fertility were observed in male and female rats at oral doses up to 40 mg/kg pioglitazone hydrochloride daily prior to and throughout mating and gestation. Pioglitazone administered to pregnant rats during organogenesis did not cause adverse developmental effects at a dose of 20 mg/kg. When pregnant rats received pioglitazone during late gestation and lactation, delayed postnatal development, attributed to decreased body weight, occurred in offspring at maternal doses of 10 mg/kg and above. In pregnant rabbits administered pioglitazone during organogenesis, no adverse developmental effects were observed at 80 mg/kg, but reduced embryofetal viability at 160 mg/kg. Pioglitazone hydrochloride was not mutagenic in a battery of genetic toxicology studies, including the Ames bacterial assay, a mammalian cell forward gene mutation assay, an in vitro cytogenetics assay using CHL cells, an unscheduled DNA synthesis assay, and an in vivo micronucleus assay.
Pioglitazone acts as an agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors increases the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, pioglitazone both enhances tissue sensitivity to insulin and reduces hepatic gluconeogenesis. Thus, insulin resistance associated with type 2 diabetes mellitus is improved without an increase in insulin secretion by pancreatic β cells.
In contrast to troglitazone, pioglitazone is not associated with an increased frequency of aminotransferase elevations during therapy. In clinical trials, ALT elevations above 3 times the ULN occurred in only 0.26% of patients on pioglitazone, compared to 0.25% of placebo recipients (and 1.9% of troglitazone recipients in similar studies). In addition, clinically apparent liver injury attributed to pioglitazone is very rare, fewer than a dozen cases having been described in the literature despite extensive use of this agent. The liver injury usually arises between 1 and 6 months after starting therapy and all patterns of serum enzymes elevations have been described including hepatocellular, cholestatic and mixed. Allergic phenomena are rare and autoantibodies have not been typically present. Cases of acute liver failure attributed to pioglitazone have been reported, usually in association with a hepatocellular pattern of injury. In most instances, recovery is complete within 2 to 3 months.
Following oral administration of pioglitazone, peak serum concentrations are observed within 2 hours (Tmax) - food slightly delays the time to peak serum concentration, increasing Tmax to approximately 3-4 hours, but does not alter the extent of absorption. Steady-state concentrations of both parent drug and its primary active metabolites are achieved after 7 days of once-daily administration of pioglitazone. Cmax and AUC increase proportionately to administered doses.
Approximately 15-30% of orally administered pioglitazone is recovered in the urine. The bulk of its elimination, then, is presumed to be through the excretion of unchanged drug in the bile or as metabolites in the feces.
来源:DrugBank
吸收、分配和排泄
分布容积
吡格列酮的平均表观分布容积为0.63 ± 0.41 L/kg。
The average apparent volume of distribution of pioglitazone is 0.63 ± 0.41 L/kg.
来源:DrugBank
吸收、分配和排泄
清除
口服给药的吡格列酮的表观清除率是5-7升/小时。
The apparent clearance of orally administered pioglitazone is 5-7 L/h.
There was no significant difference in the pharmacokinetic profile of pioglitazone in subjects with normal or with moderately impaired renal function. In patients with moderate and severe renal impairment, although mean serum concentrations of pioglitazone and its metabolites were increased, no dose adjustment is needed. After repeated oral doses of pioglitazone, mean AUC values were decreased in patients with severe renal impairment compared with healthy subjects with normal renal function for pioglitazone.
来源:Hazardous Substances Data Bank (HSDB)
安全信息
危险品标志：
C,F
安全说明：
S16,S26,S36/37,S36/37/39,S45
危险类别码：
R20/21/22,R11,R34
危险性防范说明：
P280
危险性描述：
H302,H312,H332,H351,H361
储存条件：
存于阴凉干燥处。
制备方法与用途
生物活性
Pioglitazone (U 72107) 是一种选择性过氧化物酶体增殖物激活受体γ (PPARγ) 激动剂，用于治疗糖尿病。它对全长 hPPARα 的作用较弱且仅是弱激活剂，但对全长 hPPARδ 无活性。
靶点
Target
Value
PPARγ
体外研究
Pioglitazone 主要被 CYP2C8 代谢，其次被 CYP3A4 代谢。
体内研究
在广泛前壁心肌梗死小鼠中，Pioglitazone 能显著通过超声心动图减弱左心室 (LV) 腔的扩张和功能障碍及左心室舒张末期压力。它还能部分标准化左心房 DP/DT（最大值）和 DP/DT（最小值），以及左室收缩功能，这些指标在 MI 小鼠中显著减少。
[EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
申请人：GILEAD APOLLO LLC
公开号：WO2017075056A1
公开（公告）日：2017-05-04
The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
DISUBSTITUTED TRIFLUOROMETHYL PYRIMIDINONES AND THEIR USE
申请人：BAYER PHARMA AKTIENGESELLSCHAFT
公开号：US20160221965A1
公开（公告）日：2016-08-04
The present application relates to novel 2,5-disubstituted 6-(trifluoromethyl)pyrimidin-4(3H)-one derivatives, to processes for their preparation, to their use alone or in combinations for the treatment and/or prevention of diseases, and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular for treatment and/or prevention of cardiovascular, renal, inflammatory and fibrotic diseases.
Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
申请人：Vertex Pharmaceuticals Incorporated
公开号：US20150231142A1
公开（公告）日：2015-08-20
The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
[EN] SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN<br/>[FR] COMPOSÉS DE SULFONYLE QUI INTERAGISSENT AVEC LA PROTÉINE RÉGULATRICE DE LA GLUCOKINASE
申请人：AMGEN INC
公开号：WO2013123444A1
公开（公告）日：2013-08-22
The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.
SULFOXIMINE SUBSTITUTED QUINAZOLINES FOR PHARMACEUTICAL COMPOSITIONS
申请人：BLUM Andreas
公开号：US20140135309A1
公开（公告）日：2014-05-15
This invention relates to novel sulfoximine substituted quinazoline derivatives of formula I
wherein Ar, R
1
and R
2
are as defined herein, and their use as MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) kinase inhibitors, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment or amelioration of MNK1 (MNK1a or MNK1b) and/or MNK2 (MNK2a or MNK2b) mediated disorders.
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