Benznidazole therapy is associated with an appreciable rate of serum enzyme elevations, found in at least 10% of patients. The abnormalities, however, are generally mild, transient and without accompanying symptoms or jaundice. In clinical trials there were no reported instances of clinically apparent liver injury with jaundice attributed to benznidazole. However, since its approval and more widescale use, there have been several case reports of drug rash with eosinophilia and systemic symptoms (DRESS syndrome) accompanied by serum enzyme elevations associated with benznidazole therapy, one of which was accompanied by jaundice. Furthermore, cases of immunoallergic hepatitis have been reported with other more commonly used nitroimidazoles such as metronidazole and ornidazole, some of which have been severe. Thus, benznidazole therapy has had limited clinical use, but it appears to have the potential to cause symptomatic, immunoallergic hepatitis with jaundice.
◉ Summary of Use during Lactation:Benznidazole is excreted into milk in dosages much lower than the treatment dosage for infants. Because of the low levels of benznidazole in breastmilk and safety when given directly to infants, its use is acceptable in nursing mothers.
◉ Effects in Breastfed Infants:Ten women with chronic Chagas disease received benznidazole in a median oral dose of 5.65 mg/kg twice daily for 30 days. Median infant age Ten women with chronic Chagas disease received benznidazole in a median oral dose of 5.65 mg/kg twice daily for 30 days. Median infant age was 5.2 months (range 20 days-13 months). Five children were exclusively breastfed and the others partially breastfed. None of the infants had any adverse reactions attributable to benznidazole.
A postpartum woman diagnosed with Chagas disease was treated with benznidazole 5 mg/kg daily beginning one month postpartum and continuing for 30 days. She continued to breastfeed (extent not stated) her infant. The authors reported that no adverse effects were seen in the infant.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
吸收、分配和排泄
吸收
本尼迪azole的生物利用度为91.7%，达峰时间为2.93小时。
Benznidazole has a bioavailability of 91.7% and a Tmax of 2.93 h.
来源:DrugBank
吸收、分配和排泄
消除途径
本尼尼佐拉唑的代谢物似乎主要在尿液中排泄。
The metabolites of benznidazole appear to be primarily exreted in the urine.
The invention provides inhibitors of a sterol C14-demethylase, a new series of 4- aminopyridyl-based lead inhibitors targeting Trypanosoma cruzi CYP51 (TcCYP51) developed using structure-based drug design as well as structure -property relationship (SPR) analyses. The screening hit starting point, LP 10 (KD < 42 nM; EC50 of 0.65 μΜ), has been optimized to give the potential leads that have low nanomolar binding affinity to TcCYP51 and significant activity against T. cruzi amastigotes cultured in human myoblasts. Many of the optimized compounds have improved microsome stability, and most are selective against the T. cruzi CYP51 relative to human CYPs 1A2, 2D6 and 3A4 (<50% inhibition at 1 μΜ). A rationale for the improvement of microsome stability and selectivity of inhibitors against human metabolic CYP enzymes is presented. In addition, the binding mode of several compounds of the invention with the T. brucei CYP51 (TbCYP51) ortholog has been characterized by x-ray structure analysis. Orally active compounds and their cyclodextrin complexes have been shown to be effective against Chagas-infected mice.
Amino-substituted heterocycles, compositions thereof, and methods of treatment therewith
申请人：D'Sidocky Neil R.
公开号：US20080242694A1
公开（公告）日：2008-10-02
Provided herein are Heterocyclic Compounds having the following structure:
wherein R
1
, R
2
, X, Y and Z are as defined herein, compositions comprising an effective amount of a Heterocyclic Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heterocyclic Compound to a patient in need thereof.
SELF-ASSEMBLY OF THERAPEUTIC AGENT-PEPTIDE NANOSTRUCTURES
申请人：Ohio State Innovation Foundation
公开号：US20140155577A1
公开（公告）日：2014-06-05
Disclosed are conjugates of hydrophobic drugs linked to protected or unprotected amino acids or peptides. The disclosed conjugates are amphiphilic and can self assemble into nanotubes. Nanotubes comprising the conjugates are also described and can have high loading of the drug and protect it from degradation or elimination. The nanotubes are well suited to deliver hydrophobic and unstable drugs to individuals.
[EN] SUBSTITUTED HETEROARYL COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS HÉTÉROARYLE SUBSTITUÉS ET LEURS MÉTHODES D'UTILISATION
申请人：CALITOR SCIENCES LLC
公开号：WO2015148868A1
公开（公告）日：2015-10-01
The present invention provides novel heteroaryl compounds, pharmaceutical acceptable salts and formulations thereof useful in preventing, treating or lessening the severity of a protein-mediated disease. The invention also provides pharmaceutically acceptable compositions comprising such compounds and methods of using the compositions in the treatment of protein kinase-mediated disease.
Isoindole-imide compounds and compositions comprising and methods of using the same
申请人：Muller W. George
公开号：US20070049618A1
公开（公告）日：2007-03-01
This invention relates to isoindole-imide compounds, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof. Methods of use, and pharmaceutical compositions of these compounds are disclosed.
