Certolozane is not metabolized to any significant extent.[FDA label] The beta-lactam ring of tazobactam, when administered as ceftolozane-tazobactam, is hydrolyzed to form an inactive metabolite.[FDA label]
**A note on nephrotoxicity** This drug is mainly excreted by the kidneys[A179431], and if administered to a patient with a creatinine clearance of less than 50 mL/min, may cause renal damage. Consult official product labeling for dosing adjustments in patients with renal impairment.[FDA label,A179437] **Overdose information** If an overdose occurs, discontinue the drug and follow this with supportive treatment. Dialysis may be used.[FDA label] **Use in pregnancy** Ceftolozane-tazobactam is a pregnancy category B drug, but human studies have not been performed to validate this in humans. At doses equivalent to 4-7 the standard dose administered in humans, no developmental abnormalities were seen. Since animal studies are not always predictive of drug response in humans, it is advisable to exercise caution if this drug is prescribed during pregnancy. The mother's clinical need should be assessed as well as possible risks to the fetus.[FDA label] **Use in lactation** Whether this drug is excreted in human breast milk is unknown. Caution is advised if this drug is administered during lactation, as many other drugs are known to be secreted into breast milk.[FDA label] **Carcinogenesis/mutagenesis** Formal studies have not been conducted in humans to assess mutagenicity or carcinogenicity. Studies in mice and rats did not reveal any mutagenic or carcinogenic potential, however, the potential risks resulting from long-term use have not been studied.[FDA label]
The area under the curve (AUC) of ceftolozane-tazobactam after an injected dose of 1 g/0.5 g every 8 hours for 1 day was 172 mcg•h/mL[FDA label]. The Cmax (peak concentration) and AUC are dose-dependent. The Cmax on day one of the above dose of ceftolozane-tazobactam was 69.1 mcg/mL.[FDA label]
来源:DrugBank
吸收、分配和排泄
消除途径
Ceftolozane 主要通过尿液排出。[FDA 标签，A179431]
Ceftolozane is mainly excreted in the urine.[FDA label,A179431]
来源:DrugBank
吸收、分配和排泄
分布容积
13.5 L [FDA 标签] 头孢他美唑巴坦在体内的分布迅速，并且能够很好地渗透到肺部，使其成为治疗细菌性肺炎的理想选择。[A179437]
13.5 L [FDA label] Tissue distribution of ceftalozone-tazobactam is rapid and shows good penetration into the lung, rendering it an ideal treatment for bacterial pneumonia.[A179437]
The renal clearance of was measured to be 3.41 – 6.69 L/h after a single dose of ceftolozane-tazobactam. Dose adjustments of this drug are required in patients with impaired renal function with a creatinine clearance of 50 mL/min or below. Consult official labeling for dosing adjustment guidelines.[FDA label,A179437]
[EN] SYNTHESIS OF CEPHALOSPORIN COMPOUNDS<br/>[FR] SYNTHÈSE DE COMPOSÉS DE CÉPHALOSPORINE
申请人：MERCK SHARP & DOHME
公开号：WO2016025839A1
公开（公告）日：2016-02-18
Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising a palladium-catalyzed coupling reaction. Provided herein are methods for the synthesis of cephalosporin compounds of formula (I) employing a palladium-catalyzed alkylation reaction, as well as compositions related to the same. In an aspect, provided herein is a method for preparing a compound of formula (II), or a salt thereof, comprising the step of admixing, e.g., reacting, a compound of formula (III), or a salt thereof, with a nucleophile (Nuc) in the presence of reagents comprising: (a) a palladium source; and (b) a palladium-binding ligand, to form a compound of formula (II), or a salt thereof.
Compounds of Formula (I), their preparation and use in preventing or treating bacterial infections are disclosed.
公式（I）的化合物、它们的制备以及在预防或治疗细菌感染中的应用被披露。
[EN] REACTIONS OF THIADIAZOLYL-OXIMINOACETIC ACID DERIVATIVE COMPOUNDS<br/>[FR] RÉACTIONS DE COMPOSÉS DÉRIVÉS DE L'ACIDE THIADIAZOLYL-OXIMINOACÉTIQUE
申请人：MERCK SHARP & DOHME
公开号：WO2015196077A1
公开（公告）日：2015-12-23
This disclosure relates to an improved synthesis of cephalosporin antibiotic compounds such as ceftolozane, and compositions and methods of use thereof. Thiadiazolyl-oximinoacetic acid compounds such as TATD can be reacted to yield the activated thiadiazolyl-oximinoacetic acid methanesulfonate ester compounds useful in the manufacture of cephalosporin antibiotic compounds.
This disclosure provides pharmaceutical compositions comprising ceftolozane, pharmaceutical compositions comprising ceftolozane and tazobactam, methods of preparing those compositions, and related methods and uses of these compositions.
The present invention relates to a compound of the formula [I]:
1
wherein
R
1
is lower alkyl, hydroxy(lower)alkyl or halo(lower)alkyl, and
R
2
is hydrogen or amino protecting group, or
R
1
and R
2
are bonded together and form lower alkylene or lower alkenylene;
R
3
is hydrogen or lower alkyl;
R
4
is
2
R
5
is carboxy or protected carboxy; and
R
6
is amino or protected amino,
or a pharmaceutically acceptable salt thereof, a process for preparing a compound of the formula [I], and a pharmaceutical composition comprising a compound of the formula [I] in admixture with a pharmaceutically acceptable carrier.
