Less than 1% of cefepime is metabolized in the liver. Cefepime is metabolized to N-methylpyrrolidine (NMP), which then undergoes rapid oxidation to form NMP-N-oxide, a more stable compound. NMP-N-oxide is the predominant metabolite of cefepime, while NMP and the 7-epimer of cefepime are minor byproducts. It has been suggested that flavin-containing mixed-function oxygenase mediates the oxidation of NMP to NMP-N-oxide.
参考文献：M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. 美国食品药品监督管理局批准的药物标签用于研究药物诱导的肝损伤，《药物发现今日》，16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank：按人类发展药物诱导肝损伤风险排名的最大参考药物清单。《药物发现今日》2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
References:M Chen, V Vijay, Q Shi, Z Liu, H Fang, W Tong. FDA-Approved Drug Labeling for the Study of Drug-Induced Liver Injury, Drug Discovery Today, 16(15-16):697-703, 2011. PMID:21624500 DOI:10.1016/j.drudis.2011.05.007
M Chen, A Suzuki, S Thakkar, K Yu, C Hu, W Tong. DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans. Drug Discov Today 2016, 21(4): 648-653. PMID:26948801 DOI:10.1016/j.drudis.2016.02.015
Healthy adult male volunteers (n=9) given a single intravenous infusion of 500 mg, 1 g, and 2 g of cefepime had a corresponding Cmax of 39.1, 81.7 and 163.9 μg/mL, and a corresponding AUC of 70.8, 148.5 and 284.8 h⋅μg/mL. On the other hand, healthy adult male volunteers given a single intramuscular infusion of 500 mg, 1 g, and 2 g of cefepime had a corresponding Cmax of 13.9, 29.6 and 57.5 μg/mL, a corresponding AUC of 60, 137 and 262 h⋅μg/mL, and a corresponding Tmax of 1.4, 1.6 and 1.5 h. A study in healthy adult male volunteers (n=7) that received clinically relevant doses for 9 days suggests that cefepime is not accumulated in the body. Between 250 mg and 2 g, cefepime follows a linear pharmacokinetic model, and the absolute bioavailability of cefepime in pediatric patients (n=8) given an intramuscular dose of 50 mg/kg was 82.3%.
Cefepime is mainly eliminated by the kidneys, and most of it is excreted unchanged. Approximately 85% of cefepime administered to normal subjects is excreted unchanged in urine. Less than 1% of the administered dose is recovered from urine as N-methylpyrrolidine (NMP), 6.8% as NMP-N-oxide, and 2.5% as an epimer. Dosage adjustments are required in patients with renal dysfunction or those undergoing hemodialysis, due to the importance of renal excretion in eliminating cefepime.
来源:DrugBank
吸收、分配和排泄
分布容积
头孢匹胺的平均稳态分布容积为18.0升。在儿科患者中，平均稳态分布容积为0.3升/千克。
The average steady-state volume of distribution of cefepime is 18.0 L. In pediatric patients, the average steady-state volume of distribution is 0.3 L/kg.
Cefepime has a total body clearance of 120 mL/min in healthy volunteers, and in pediatric patients, the average total body clearance is 3.3 mL/min/kg. In geriatric patients (65 years of age and older) and patients with abnormal renal function, cefepime total body clearance decreases proportionally with creatinine clearance.
[EN] DERIVATIVES OF AMANITA TOXINS AND THEIR CONJUGATION TO A CELL BINDING MOLECULE<br/>[FR] DÉRIVÉS DE TOXINES D'AMANITES ET LEUR CONJUGAISON À UNE MOLÉCULE DE LIAISON CELLULAIRE
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2017046658A1
公开（公告）日：2017-03-23
Derivatives of Amernita toxins of Formula (I), wherein, formula (a) R 1, R 2, R 3, R 4, R 5, R 6, R 7, R 8, R 9, R 10, X, L, m, n and Q are defined herein. The preparation of the derivatives. The therapeutic use of the derivatives in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.
[EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020257998A1
公开（公告）日：2020-12-30
Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.
[EN] CROSS-LINKED PYRROLOBENZODIAZEPINE DIMER (PBD) DERIVATIVE AND ITS CONJUGATES<br/>[FR] DÉRIVÉ DE DIMÈRE DE PYRROLOBENZODIAZÉPINE RÉTICULÉ (PBD) ET SES CONJUGUÉS
申请人：HANGZHOU DAC BIOTECH CO LTD
公开号：WO2020006722A1
公开（公告）日：2020-01-09
A novel cross-linked cytotoxic agents, pyrrolobenzo-diazepine dimer (PBD) derivatives, and their conjugates to a cell-binding molecule, a method for preparation of the conjugates and the therapeutic use of the conjugates.
[EN] COMPOSITIONS AND METHODS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS ET MÉTHODES POUR LE TRAITEMENT D'INFECTIONS BACTÉRIENNES
申请人：CIDARA THERAPEUTICS INC
公开号：WO2018006063A1
公开（公告）日：2018-01-04
Compositions and methods for the treatment of bacterial infections include compounds containing dimers of cyclic heptapeptides conjugated to one or more monosaccharide or oligosaccharide moieties. In particular, compounds can be used in the treatment of bacterial infections caused by Gram-negative bacteria.
[EN] QUINOLONE DERIVATIVES AS ANTIBACTERIALS<br/>[FR] DÉRIVÉS DE QUINOLONE COMME ANTIBACTÉRIENS
申请人：NOVARTIS AG
公开号：WO2016020836A1
公开（公告）日：2016-02-11
This invention is in the field of medicinal chemistry and relates to compounds, and pharmaceutical compositions thereof, that inhibit bacterial gyrase. The compounds are useful as inhibitors of bacterial gyrase activity and bacterial infections, and have the structure of Formula (I) as further described herein. The invention further provides pharmaceutical compositions comprising a compound of Formula (I) and methods of using the compounds and compositions to treat bacterial infections.
