IDENTIFICATION AND USE: Gentamicin sulfate is an aminoglycoside antibiotic. Gentamicin is widely used in the treatment of severe infections. It is active against many strains of Gram-negative bacteria and Streptococus aureus. It is inactive against anaerobes and poorly active against Streptococus hemolyticus and Pneumococcus. HUMAN EXPOSURE AND TOXICITY: Main risks and target organs: The main toxic effects are vestibular damage, deafness and renal dysfunction. The damage on the vestibular portion of the eighth cranial nerve appears to be greater than that on the cochlear portion. The main target organs are the eighth cranial nerves and the kidneys. Damage to eighth cranial nerve (both divisions) resulting in tinnitus, deafness, nausea, vomiting, vertigo, dizziness and nystagmus, and nephrotoxicity causing acute tubular necrosis resulting in renal failure. Loss of hearing, dizziness, vertigo, ataxia, nausea, vomiting and renal impairment developing in a patient on gentamicin therapy suggests a diagnosis of gentamicin toxicity. Other toxic features are muscular paralysis and respiratory depression. As gentamicin accumulates in the renal cortex, a critical concentration is reached when the concentrating ability of the kidney becomes impaired. Nephrotoxicity appears to be related to the duration for which the trough serum concentration exceeds 2 ug/ml. The exact mechanism of toxicity is unknown. Ototoxicity and vestibular toxicity seem most highly correlated with elevated peak concentrations (greater than 10 ug/mL) of gentamicin. Gentamicin accumulates in endolymph and perilymph and progressive destruction of ventricular and cochlear cells occurs. Repeated courses of gentamicin may produce progressive destruction of cells leading to deafness. Gentamicin appears to damage the vestibular portion more than the cochlear portion. Neuromuscular blockade with acute muscular paralysis and apnea may occur rarely. Most episodes have occurred in association with anesthesia or administration of other neuromuscular blockers but may also occur after intrapleural or intraperitoneal instillation of large doses of gentamicin or other aminoglycosides. This phenomenon may occur after intravenous or intramuscular administration. ANIMAL STUDIES: Clinical signs of intoxication in rodents included convulsions, prostration, hypoactivity, polydipsia, dyspnoea and ataxia. Dogs exhibited muscle tremors, salivation, and anorexia. Histopathological examination of kidneys from dogs that died up to 13 days after dosing revealed necrosis of the proximal convoluted tubule. Groups of 3 female Rhesus monkeys were injected i.m. with doses of 0, 6 or 30 mg/kg bw/day gentamicin in an aqueous vehicle for 3 weeks. Adverse clinical signs were limited to the 30 mg/kg bw/day group, which included pronounced facial paling and ptosis, markedly disturbed equilibrium from day 20, and depressed food intake and body- weight gain from week 2 onwards. Electron microscopy of renal tubules from the 30 mg/kg bw/day monkeys revealed myeloid bodies present in both tubular cells and lumen, increased phagosomes, disappearance of brush borders and sloughing of epithelial cells from the basement membrane. Groups of beagle dogs (4/sex/group) were administered oral doses of 0, 2, 10, or 60 mg/kg bw/day gentamicin in capsules for 14 weeks. Emesis and diarrhoea were observed occasionally in treated dogs. The only postmortem change was interstitial nephritis observed in 2 animals in the high-dose group. Gentamicin had negative effects on sperm parameters and testis apoptosis in rats. No treatment-related changes in pregnancy rate, litter size and weight, prenatal mortality or fetal abnormalities were reported in 2 generation study in rats. Gentamicin was tested in vitro for its ability to induce forward gene mutation in Chinese hamster ovary cells at concentrations of 128-5000 ug/mL and chromosomal aberrations in these cells at concentrations of 800-5000 ug/mL, both with and without metabolic activation. It was also tested in vivo for its ability to induce nuclear anomalies in mouse bone-marrow cells at intravenous doses of 20-80 mg/kg bw, the highest dose being the maximum tolerated dose. There was no indication of mutagenic activity.
Intravenous and intramuscular therapy with gentamicin has been linked to mild and asymptomatic elevations in serum alkaline phosphatase levels, but rarely affects aminotransferase levels or bilirubin, and changes resolve rapidly once gentamicin is stopped. Only isolated case reports of acute liver injury with jaundice have been associated with aminoglycoside therapy including gentamicin, most of which are not very convincing. The hepatic injury described in these reports is typically mixed but can evolve into a cholestatic hepatitis. The latency to onset is rapid, occurring within 1 to 3 weeks and is typically associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Aminoglycosides are not listed or mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to gentamicin is rare if it occurs at all.
◉ Summary of Use during Lactation:Gentamicin is poorly excreted into breastmilk. Newborn infants apparently absorb small amounts of gentamicin, but their serum levels with three times daily dosages are far below those attained when treating newborn infections and systemic effects of gentamicin are unlikely. Older infants would be expected to absorb even less gentamicin. Because there is little variability in the milk gentamicin levels during multiple daily dose regimens, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Data are not available with single daily dose regimens. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
Maternal use of an ear drop or eye drop that contains gentamicin presents little or no risk for the nursing infant.
◉ Effects in Breastfed Infants:Bloody stools in one 5-day-old infant were possibly caused by concurrent maternal administration of clindamycin and gentamicin.
A 2-month-old infant breastfed since birth. His mother had taken many medications during pregnancy, but she did not recall their identity. She developed mastitis and was treated with amoxicillin-clavulanic acid 1 gram orally every 12 hours and gentamicin 160 mg intramuscularly once daily. The infant was breastfed for 10 minutes starting 15 minutes after the first dose of both drugs. About 20 minutes later, the infant developed a generalized urticaria which disappeared after 30 minutes. A few hours later, the infant breastfed again and the urticaria reappeared after 15 minutes and disappeared after an hour. After switching to formula feeding and no further infant exposure to penicillins, the reaction did not reappear with follow-up to 16 months of age. The adverse reaction was probably caused by the antibiotics in breastmilk. The drug that caused the reaction cannot be determined, but it was most likely the amoxicillin-clavulanic acid.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
来源:Drugs and Lactation Database (LactMed)
毒理性
副作用
皮肤致敏剂 - 一种可以诱导皮肤产生过敏反应的制剂。
Skin Sensitizer - An agent that can induce an allergic reaction in the skin.
来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases
毒理性
相互作用
一项体外研究表明，阿糖胞苷可能拮抗庆大霉素对肺炎克雷伯菌的活性。
One in vitro study indicates that cytarabine may antagonize the activity of gentamicin against Klebsiella pneumoniae.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
/牛奶/ 庆大霉素在肌内注射后分布到牛奶中。
/MILK/ Gentamicin is distributed into milk following IM administration.
Gentamicin is distributed into cerebrospinal fluid (CSF) in low concentrations following IM or IV administration. CSF concentrations of gentamicin following intrathecal administration depend on the dose administered, the site of injection, the volume in which the dose is diluted, and the presence or absence of obstruction to CSF flow. There may be considerable interpatient variation in concentrations achieved. In one study, intrathecal administration of 4 mg of gentamicin resulted in CSF concentrations of the drug of 19-46 ug/mL for 8 hours and less than 3 ug/mL at 20 hours. Gentamicin crosses the placenta.
Following parenteral administration of usual dosages of gentamicin, the drug can be detected in lymph, subcutaneous tissue, lung, sputum, and bronchial, pleural, pericardial, synovial, ascitic, and peritoneal fluids. Concentrations in bile may be low, suggesting minimal biliary excretion. In patients with ventilator-associated pneumonia receiving IV gentamicin (240 mg once daily), drug concentrations in alveolar lining fluid were 32% of serum concentrations and averaged 4.24 ug/mL 2 hours after a dose. Only minimal concentrations of gentamicin are attained in ocular tissue following IM or IV administration.
Accumulation of gentamicin does not appear to occur in patients with normal renal function receiving 1-mg/kg doses every 8 hours for 7-10 days. However, accumulation may occur with higher doses and/or when the drug is given for prolonged periods, especially in patients with renal impairment.
Inhibitors of aminoglycoside 6'-N-acetyltransferases, compositions and uses thereof
申请人：Auclair Karine
公开号：US20060211634A1
公开（公告）日：2006-09-21
The present invention relates to inhibitors of aminoglycoside 6′-N-acetyltransferases of Formula I:
R—X—Y-Z Formula I
wherein:
R is selected from the group consisting of:
R
1
is selected from the group consisting of OH and
R
2
is selected from the group consisting of OH and
R
3
is selected from the group consisting of NH
2
and OH;
R
4
is selected from the group consisting of NH
2
and
R
5
is selected from the group consisting of OMe, OEt OPr, and O-iPr; X is selected from the group consisting of NH and O;
Y is selected from the group consisting of:
R
6
is selected from the group consisting of OH, CH
3
, and OCH
3
; n is an integer ranging from 1 to 10; and
Z is selected from the group consisting of:
and
R
7
is selected from the group consisting of OH, OMe, OEt OPr, O-iPr, O-tBu and
[EN] REGIOSELECTIVE DIAZOTATION OF AMINOGLYCOSIDES<br/>[FR] DIAZOTATION RÉGIOSÉLECTIVE DES AMINOGLYCOSIDES
申请人：UNIV GRONINGEN
公开号：WO2013191550A1
公开（公告）日：2013-12-27
The invention relates to the field of chemical derivatization. In particular, it relates to modified aminoglycosides, such as antibiotics, and methods for producing them. Provided is a method for the regioselective diazotation of a desoxy-streptamine- substituted aminoglycoside, comprising contacting the aminoglycoside with imidazole- -sulfonyl azide hydrochloride under neutral p H conditions to allow for the conversion of the single amine group at the 3-C position of the desoxy-streptamine ring into an azide group. Also provided are novel antibiotic compounds.
[EN] ANIONIC CONJUGATES OF GLYCOSYLATED BACTERIAL METABOLITE<br/>[FR] CONJUGUÉS ANIONIQUES D'UN MÉTABOLITE BACTÉRIEN GLYCOSYLÉ
申请人：GLYCAN BIOSCIENCES PTY LTD
公开号：WO2010037179A1
公开（公告）日：2010-04-08
The invention relates to anionic conjugates of glycosylated bacterial metabolites that may be used to mimic the structure and/or activity of the anionic bioactive molecules known as glycosaminoglycans (GAGs). The invention also relates to processes for the preparation of the conjugates. Such conjugates are useful in the prophylaxis and/or treatment of disease conditions and in particular chronic disease conditions such as inflammatory (including allergic) diseases, metastatic cancers and infection by pathogenic agents including bacteria, viruses or parasites.
Novel aminoglycosides and uses thereof in the treatment of genetic disorders
申请人：Bassov Timor
公开号：US20090093418A1
公开（公告）日：2009-04-09
A new class of paromomycin-derived aminoglycosides, which exhibit efficient stop-codon mutation suppression activity, low toxicity and high selectivity towards eukaryotic cells are provided. Also provided are chemical and chemo-enzymatic processes of preparing these paromomycin-derived aminoglycosides and intermediates thereof, as well as pharmaceutical compositions containing the same, and uses thereof in the treatment of genetic disorders.
ENDOPROSTHESIS HAVING AND ACTIVE SUSBTANCE COATING
申请人：Hemoteq AG
公开号：US20170014364A1
公开（公告）日：2017-01-19
The present invention relates to an endoprosthesis with a drug coating comprising or consisting of at least one antibiotic agent and at least one further substance having the following general
