Ciprofloxacin hydrochloride ophthalmic solution should be stored in tight, light-resistant containers at 2-25 °C. When stored as directed, the commercially available ophthalmic solution has an expiration date of 24 months following the date of manufacture. Ciprofloxacin hydrochloride ophthalmic ointment should be stored at 2-25 °C. Ciprofloxacin hydrochloride and hydrocortisone otic suspension should be stored in light-resistant containers below 25 °C; freezing should be avoided. Ciprofloxacin hydrochloride and dexamethasone otic suspension should be stored at 15-30 °C and protected from light; freezing should be avoided.
分解：
When heated to decomposition material emits toxic fumes of /nitrogen oxides and hydrogen fluoride/.
Ciprofloxacin is primarily metabolized by CYP1A2. The primary metabolites oxociprofloxacin and sulociprofloxacin make up 3-8% of the total dose each. Ciprofloxacin is also converted to the minor metabolites desethylene ciprofloxacin and formylciprofloxacin. These 4 metabolites account for 15% of a total oral dose. There is a lack of available data on the enzymes and types of reactions involved in forming these metabolites.
The drug is partially metabolized in the liver by modification of the piperazinyl group to at least 4 metabolites. These metabolites, which have been identified as desethyleneciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), and N-formylciprofloxacin (M4), have microbiologic activity that is less than that of the parent drug but may be similar to or greater than that of some other quinolones (e.g., M3 and M4 are comparable to norfloxacin for certain organisms).
Hepatic. Four metabolites have been identified in human urine which together account for approximately 15% of an oral dose. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin.
Route of Elimination: Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug.
Half Life: 4 hours
The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, strand supercoiling repair, and recombination.
Ciprofloxacin like other fluoroquinolones is associated with a low rate (1% to 3%) of serum enzyme elevations during therapy. These abnormalities are generally mild, asymptomatic and transient, resolving even with continuation of therapy. More importantly, ciprofloxacin has been linked to rare, but occasionally severe and even fatal cases of acute liver injury. The time to onset is typically short (2 days to 2 weeks) and the presentation is often abrupt with nausea, fatigue and abdominal pain, followed by dark urine and jaundice. The pattern of serum enzyme elevations can be either hepatocellular or cholestatic; cases with the shorter times to onset usually being more hepatocellular with markedly elevated ALT levels, and occasionally with rapid worsening of prothrombin time and early signs of hepatic failure. The onset of illness also may occur a few days after the medication is stopped. Cases with a cholestatic pattern of enzymes may run a prolonged course, but are usually self-limiting. Nevertheless, chronic cholestasis and vanishing bile duct syndrome have been reported with ciprofloxacin and other fluoroquinolones. Finally, the enzyme pattern can be initially hepatocellular and then evolve during the course of illness from a hepatocellular into a mixed or cholestatic pattern. Many (but not all) cases have had allergic manifestations with fever, rash and eosinophilia. Autoantibodies are usually not present.
A 250mg oral dose of ciprofloxacin reaches an average maximum concentration of 0.94mg/L in 0.81 hours with an average area under the curve of 1.013L/h\*kg. The FDA reports an oral bioavailability of 70-80% while other studies report it to be approximately 60%. An early review of ciprofloxacin reported an oral bioavailability of 64-85% but recommends 70% for all practical uses.
27% of an oral dose was recovered unmetabolized in urine compared to 46% of an intravenous dose. Collection of radiolabelled ciprofloxacin resulted in 45% recovery in urine and 62% recovery in feces.
Cirpofloxacin follws a 3 compartment distribution model with a central compartment volume of 0.161L/kg and a total volume of distribution of 2.00-3.04L/kg.
The average renal clearance after a 250mg oral dose is 5.08mL/min\*kg. Following a 100mg intravenous dose, the average total clearance is 9.62mL/min\*kg, average renal clearance is 4.42mL/min\*kg, and average non renal clearance is 5.21mL/min\*kg.
Based on population pharmacokinetics, bioavailability of ciprofloxacin oral suspension in children is approximately 60%. Following a single oral dose of 10 mg/kg of ciprofloxacin given as the oral suspension to children 4 months to 7 years of age, the mean peak plasma concentration was 2.4 ug/mL. There was no apparent age dependence and no increase in peak plasma concentrations following multiple doses.
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] ANTIBACTERIAL 8-PHENYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE DERIVATIVES<br/>[FR] DÉRIVÉS ANTIBACTÉRIENS DE 8-PHÉNYLAMINO-3-(PYRAZOL-4-YL)IMIDAZO[1,2-A]PYRAZINE
申请人：HOFFMANN LA ROCHE
公开号：WO2021219578A1
公开（公告）日：2021-11-04
The invention provides novel imidazopyrazine derivatives having the general formula (I), wherein X and R3 to R9 are as described herein or pharmaceutically acceptable salts thereof, wherein X and R3 to R9 are as defined herein. Further provided are pharmaceutical compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds as medicaments, in particular methods of using the compounds as antibiotics for the treatment or prevention of bacterial infections and resulting diseases.
[EN] HIGHLY 6-SUBSTITUTED -2,4-DIAMINOPYRIMIDINES AS INHIBITORS OF ANTHRAX<br/>[FR] 2,4-DIAMINOPYRIMIDINES HAUTEMENT SUBSTITUÉES EN POSITION 6 EN TANT QU'INHIBITEURS DE L'ANTHRAX
申请人：UNIV OKLAHOMA STATE
公开号：WO2013138787A1
公开（公告）日：2013-09-19
2,4-diaminopyrimidine compounds of generic Formula 1, where R and R' may be the same or different and are independently selected from: C1-C6 alkyl or alkenyl groups with 1, 2, 3, 4, 5 or 6 carbon atoms, which may be: branched or unbranched; saturated or unsaturated; and may or may not be substituted, are used to treat anthrax.
Tricyclic compounds, protected intermediates thereof, and methods for inhibition of HIV-integrase are disclosed.
三环化合物，其受保护的中间体，以及用于抑制HIV整合酶的方法被披露。
[EN] OXAZOLIDINONE COMPOUNDS AND METHODS OF USE THEREOF AS ANTIBACTERIAL AGENTS<br/>[FR] COMPOSÉS OXAZOLIDINONE ET PROCÉDÉS D'UTILISATION DE CES DERNIERS EN TANT QU'AGENTS ANTIBACTÉRIENS
申请人：MERCK SHARP & DOHME
公开号：WO2017066964A1
公开（公告）日：2017-04-27
The present invention relates to oxazolidinone compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, E, and R1 are as defined herein. The present invention also relates to compositions which comprise at least one oxazolidinone compound of the invention. The invention also provides methods for inhibiting growth of mycobacterial cells as well as a method of treating mycobacterial infections by Mycobacterium tuberculosiscomprising administering a therapeutically effective amount of an oxazolidinone of the invention and/or apharmaceutically acceptable salt thereof, or a composition comprising such compound and/or salt.
