Metabolized primarily in the liver where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxypropafenone and N-depropylpropafenone. These metabolites have antiarrhythmic activity comparable to propafenone but are present in concentrations less than 25% of propafenone concentrations.
In individuals with the extensive-metabolizer phenotype, propafenone is metabolized in the liver to 2 active metabolites and at least 9 additional metabolites. The 2 active metabolites, 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP), are formed through hydroxylation and dealkylation of the parent drug. Propafenone hydroxylation via cytochrome CYP2D6, a cytochrome P-450 isoenzyme under genetic control, produces 5-OHP. Formation of NDPP is catalyzed by different isoenzymes, cytochrome CYP1A2 and CYP3A4. Differences in metabolism between R- and S-propafenone related to stereoselective interaction with the CYP2D6 isoenzyme have been observed in animals and humans receiving single enantiomers of the drug. Following a 250 mg oral dose of R- or S-propafenone hydrochloride administered to adults with the extensive-metabolizer phenotype, the mean values for elimination half-life, clearance, and volume of distribution for R-propafenone were smaller than those for S-propafenone, while AUC was larger; however, these stereospecific effects were not observed in an adult with the poor-metabolizer phenotype who received the separate drug enantiomers. In vitro and in vivo studies indicate that the R-enantiomer is cleared faster than the S-enantiomer via the 5-hydroxylation pathway (CYP2D6). This results in a higher ratio of the S-enantiomer to R-enantiomer at steady state. Although the enantiomers have equivalent sodium-channel blocking potency, the S-enantiomer is a more potent beta-adrenergic antagonist than the R-enantiomer. Following administration of propafenone hydrochloride (immediate-release tablets or extended-release capsules), the observed ratio of S-enantiomer to R-enantiomer (S/R ratio) for AUC was approximately 1.7. The S/R ratios after administration of 225, 325, or 425 mg extended-release capsules were independent of dose. In addition, similar S/R ratios were observed among metabolizer genotypes and following long-term administration
There are two principal patterns of propafenone metabolism. These patterns are genetically determined by an individual's ability to metabolize the drug via a hepatic oxidation pathway. The ability to oxidatively metabolize propafenone is dependent on an individual's ability to metabolize debrisoquin (debrisoquin phenotype). The debrisoquin phenotype or the observed pattern of propafenone metabolites may be used to determine an individual's metabolic phenotype for propafenone. Individuals who extensively metabolize propafenone via the oxidation pathway exhibit the extensive-metabolizer phenotype, while those who have an impaired ability to metabolize the drug by this pathway exhibit the poor-metabolizer phenotype. Approximately 90-95% of Caucasians exhibit the extensive-metabolizer phenotype, with the remainder being poor metabolizers. Propafenone metabolism in patients with the poor-metabolizer phenotype is characterized by a linear dose-concentration relationship and a relatively long terminal elimination half-life; these individuals have increased plasma propafenone concentrations relative to individuals with the extensive-metabolizer phenotype and are more likely to experience beta-adrenergic blocking and adverse effects of the drug.
来源:Hazardous Substances Data Bank (HSDB)
代谢
普罗帕封已知的人体代谢物包括N-去丙基普罗帕封和5-羟基普罗帕封。
Propafenone has known human metabolites that include N-Despropylpropafenone and 5-Hydroxypropafenone.
In clinical trials, propafenone was associated with a low rate of serum aminotransferase and alkaline phosphatase elevations. Since its approval and more widescale use, propafenone has been linked to rare instances of clinically apparent liver injury, at least a dozen cases of which have been reported in the literature. Patients usually present with symptoms of jaundice and pruritus 2 to 8 weeks after starting propafenone, and the pattern of serum enzyme elevations are typically mixed (Case 1) or cholestatic (Case 2). Immunoallergic and autoimmune features are uncommon. While the jaundice can be prolonged, patients typically recover in 1 to 3 months and there have been no instances of acute liver failure, chronic hepatitis or vanishing bile duct syndrome attributed to its use.
Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).
来源:DrugBank
吸收、分配和排泄
消除途径
大约50%的普罗帕封代谢物在服用即释片后通过尿液排出。
Approximately 50% of propafenone metabolites are excreted in the urine following administration of immediate release tablets.
In patients with ventricular arrhythmias and the extensive-metabolizer phenotype receiving 337.5, 450, 675, or 900 mg of propafenone hydrochloride daily (immediate-release tablets), the proportions of 5-hydroxypropafenone (5-OHP) to propafenone in plasma were 45, 40, 24, or 19%, respectively, while a subset of patients with the poor-metabolizer phenotype had higher relative plasma concentrations of the parent drug at each dosage and no detectable 5-OHP. Ratios of N-depropylpropafenone (NDPP) to propafenone are similar in extensive and poor metabolizers (approximately 10 and 6%, respectively). In poor metabolizers, NDPP is the principal metabolite and 5-OHP may not be detectable. Following oral administration of propafenone hydrochloride 300 mg (immediate-release tablets) every 8 hours for 14 days, plasma propafenone, 5-OHP, and NDPP concentrations averaged 1010, 174, and 179 ng/mL, respectively, in healthy individuals with the extensive-metabolizer phenotype. In an individual presumed to have the poor-metabolizer phenotype, plasma concentrations of propafenone, 5-OHP, and NDPP concentrations were 1048, undetectable, and 219 ng/mL, respectively, following oral administration of immediate-release tablets. Following administration of extended-release capsules of propafenone hydrochloride, plasma concentrations of 5-OHP and NDPP are generally less than 40 and 10% of plasma propafenone concentrations, respectively.
The pattern of plasma concentrations of propafenone and its metabolites observed in an individual patient with long-term oral propafenone therapy depends principally on the genetically determined metabolizer phenotype and, to a lesser extent, on hepatic blood flow and enzyme function. Following oral administration of propafenone (immediate-release tablets), steady-state plasma concentrations of the parent drug and its metabolites are attained within 4-5 days in individuals with normal hepatic and renal function. Plasma concentrations of 5-hydroxypropafenone (5-OHP) and N-depropylpropafenone (NDPP) generally average less than 20% those of propafenone. Poor metabolizers achieve plasma propafenone concentrations 1.5-2 times higher than those of extensive metabolizers at propafenone hydrochloride dosages of 675-900 mg (immediate-release tablets) daily; at lower dosages, poor metabolizers may attain plasma propafenone concentrations more than fivefold higher than those of extensive metabolizers.
CYCLODEXTRIN-BASED POLYMERS FOR THERAPEUTIC DELIVERY
申请人：Cerulean Pharma Inc.
公开号：US20130196906A1
公开（公告）日：2013-08-01
Provided are methods relating to the use of CDP-therapeutic agent conjugates for the treatment of a disease or disorder, e.g., autoimmune disease, inflammatory disease, central nervous system disorder, cardiovascular disease, or metabolic disorder. Also provided are CDP-therapeutic agent conjugates, particles comprising CDP-therapeutic agent conjugates, and compositions comprising CDP-therapeutic agent conjugates.
A JNK inhibitor containing a compound having an isoquinolinone skeleton or a salt thereof, such as a compound represented by the formula
wherein ring A and ring B are each an optionally substituted benzene ring, X is -O-, -N=, -NR3- or -CHR3-, R2 is an acyl group, an optionally esterified or thioesterified carboxyl group, an optionally substituted carbamoyl group or an optionally substituted amino group and the like, a broken line shows a single bond or a double bond, and R1 is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like, and the like.
Carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones and the use thereof
申请人：CoCensys, Inc.
公开号：US20020061886A1
公开（公告）日：2002-05-23
This invention is related to carbocyclic and heterocyclic substituted semicarbazones and thiosemicarbazones represented by Formula I:
1
or a pharmaceutically acceptable salt or prodrug thereof, wherein:
Y is oxygen or sulfur; R
1
, R
21
, R
22
and R
23
are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl; or R
22
and R
23
, together with the N, form a heterocycle; A
1
and A
2
are independently aryl, heteroaryl, saturated or partially unsaturated carbocycle or saturated or partially unsaturated heterocycle, any of which is optionally substituted; X is one or O, S, NR
24
, CR
25
R
26
, C(O), NR
24
C(O), C(O)NR
24
, SO, SO
2
or a covalent bond; where R
24
, R
25
and R
26
are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, haloalkyl, aryl, aminoalkyl, hydroxyalkyl, alkoxyalkyl or carboxyalkyl. The invention also is directed to the use of carbocycle and heterocycle substituted semicarbazones and thiosemicarbazones for the treatment of neuronal damage following global and focal ischemia, for the treatment or prevention of neurodegenerative conditions such as amyotrophic lateral sclerosis (ALS), for the treatment and prevention of otoneurotoxicity and eye diseases involving glutamate toxicity and for the treatment, prevention or amelioration of pain, as anticonvulsants, and as antimanic depressants, as local anesthetics, as antiarrhythmics and for the treatment or prevention of diabetic neuropathy and urinary incontinence.
This invention relates to compounds of the formula (I):
wherein R
1
, R
2
, R
3
, A and m are each as described herein or a pharmaceutically acceptable salt or solvate thereof, and compositions containing such compounds and the use of such compounds in the treatment of a condition mediated by 5-HT
4
receptor activity such as, but not limited to, gastroesophageal reflux disease, gastrointestinal disease, gastric motility disorder, non-ulcer dyspepsia, functional dyspepsia, irritable bowel syndrome (IBS), constipation, dyspepsia, esophagitis, gastroesophageral disease, nausea, central nervous system disease, Alzheimer's disease, cognitive disorder, emesis, migraine, neurological disease, pain, cardiovascular disorders such as cardiac failure and heart arrhythmia, diabetes and apnea syndrome.
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