Clindamycin undergoes hepatic metabolism mediated primarily by CYP3A4 and, to a lesser extent, CYP3A5. Two inactive metabolites have been identified - an oxidative metabolite, clindamycin sulfoxide, and an N-demethylated metabolite, N-desmethylclindamycin.
Clindamycin is partially metabolized to bioactive and inactive metabolites. The major bioactive metabolites are clindamycin sulfoxide and N-demethyl-clindamycin which are excreted in urine, bile, and feces. Within 24 hours, approximately 10% of an oral dose of clindamycin is excreted in urine and 3.6% is excreted in feces as active drug and metabolites; the remainder is excreted as inactive metabolites.
Only about 10% of the clindamycin admin is excreted unaltered in urine, and small quantities are found in feces ... Clindamycin is inactivated by metabolism to N-demethylclindamycin and clindamycin sulfoxide, which are excreted in the urine and bile.
Hepatic
Route of Elimination: Approximately 10% of the bioactivity is excreted in the urine and 3.6% in the feces; the remainder is excreted as bioinactive metabolites.
Half Life: 2.4 hours
Systemic/vaginal clindamycin inhibits protein synthesis of bacteria by binding to the 50S ribosomal subunits of the bacteria. Specifically, it binds primarily to the 23s RNA subunit. Topical clindamycin reduces free fatty acid concentrations on the skin and suppresses the growth of Propionibacterium acnes (Corynebacterium acnes) , an anaerobe found in sebaceous glands and follicles.
Clindamycin has been linked to two forms of hepatotoxicity: transient serum aminotransferase elevations usually occurring after several days of high intravenous doses; and, an acute, idiosyncratic liver injury that arises within 1 to 3 weeks of starting therapy and is typically mild and self-limited.
High doses of intravenous clindamycin can be accompanied by elevations in serum ALT levels in the range of 2 to 10 times the upper limit of normal starting after 5 to 15 days of therapy in a manner similar to what occurs with intravenous oxacillin therapy (Case 1). Symptoms, jaundice, and alkaline phosphatase elevations are mild if they occur at all (Case 2), and aminotransferase levels rapidly fall into the normal range (in 1 to 2 weeks) upon stopping clindamycin or switching to lower doses or to oral formulations with which it rarely occurs.
Clindamycin therapy has also been linked to a clinically apparent, idiosyncratic liver injury that arises between 1 to 3 weeks after starting either oral or parenteral therapy (Case 3). The pattern of serum enzyme elevations is typically hepatocellular or mixed, but can be cholestatic. Allergic manifestations such as rash, fever and eosinophilia are typical, but often are not prominent and are not present in all cases. Autoantibodies are generally not present. The acute liver injury may accompany other signs of hypersensitivity such as Stevens Johnson syndrome or other severe skin reactions. The liver injury is usually mild-to-moderate in severity and resolves rapidly with stopping. However, fatal instances have been reported.
Likelihood score: B (highly likely cause of clinically apparent liver injury).
来源:LiverTox
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
◉ Summary of Use during Lactation:Clindamycin has the potential to cause adverse effects on the breastfed infant's gastrointestinal flora. If oral or intravenous clindamycin is required by a nursing mother, it is not a reason to discontinue breastfeeding, but an alternate drug may be preferred. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.
Vaginal application is unlikely to cause infant side effects, although about 30% of a vaginal dose is absorbed. Infant side effects are unlikely with topical administration for acne; however, topical application to the breast may increase the risk of diarrhea if it is ingested by the infant. Only water-miscible cream, foam, gel or liquid products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.
◉ Effects in Breastfed Infants:Bloody stools in a 5-day-old breastfed infant were possibly caused by concurrent maternal clindamycin 600 mg intravenously every 6 hours and gentamicin 80 mg intravenously every 8 hours. The infant's stools were reported to have normal flora and the stools became guaiac negative 24 hours after discontinuation of breastfeeding. On day 6 of age, the infant resumed breastfeeding after discontinuation of maternal antibiotics with no further difficulties.
◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.
◈ What is clindamycin?
Clindamycin is an antibiotic used to treat or prevent bacterial infections. It can be taken by mouth (oral), used on the skin (topical), or given by IV (intravenous or by needle into a vein).Sometimes when people find out they are pregnant, they think about changing how they take their medication, or stopping their medication altogether. However, it is important to talk with your healthcare providers before making any changes to how you take this medication. Your healthcare providers can talk with you about the benefits of treating your condition and the risks of untreated illness during pregnancy.
◈ I take clindamycin. Can it make it harder for me to get pregnant?
It is not known if clindamycin can make it harder to get pregnant.
◈ Does taking clindamycin increase the chance for miscarriage?
Miscarriage can occur in any pregnancy. One study involving 249 women who had a vaginal bacterial infection found that clindamycin treatment reduced the chances of late miscarriage and preterm (early) births.
◈ Does taking clindamycin increase the chance of birth defects?
Every pregnancy starts out with a 3-5% chance of having a birth defect. This is called the background risk.It is unlikely that using clindamycin increases the chance of birth defects. Several human studies as well as animal studies have not shown an increased chance of birth defects.When clindamycin is used on the skin (topical use), only small amounts pass through skin and get into the bloodstream. This means a pregnancy would be exposed to only a very small amount of the medicine. Since available information about vaginal and oral clindamycin (both higher absorptions compared to topical use) does not find an increased chance of birth defects, it is also unlikely that using topical clindamycin increases the chance of birth defects.
◈ Does taking clindamycin in pregnancy increase the chance of other pregnancy related problems?
Several studies have not found an increased chance of pregnancy complications from clindamycin use in the second or third trimester.
◈ Does taking clindamycin in pregnancy affect future behavior or learning for the child?
Studies have not been done to see if clindamycin can cause behavior or learning issues for the child.
◈ Breastfeeding while taking clindamycin:
Clindamycin gets into breastmilk in small amounts when women are given clindamycin orally (by mouth) or intravenously (IV). In those situations, clindamycin might cause some gastrointestinal (GI) effects in a breastfeeding (e.g. nausea, diarrhea, stomach pain, vomiting, diaper rash, thrush, or rarely bloody stools). Topical application (to the skin) has minimal absorption into your circulation and are unlikely to end up in breast milk in amounts that might cause side effects in your baby. If you notice any symptoms in your child, contact their healthcare provider. Be sure to talk to your healthcare provider about all of your breastfeeding questions.
◈ If a male takes clindamycin, could it affect fertility (ability to get partner pregnant) or increase the chance of birth defects?
Studies have not been done to see if clindamycin could affect male fertility or increase the chance of birth defects. In general, exposures that fathers or sperm donors have are unlikely to increase the risks to a pregnancy. For more information, please see the MotherToBaby fact sheet Paternal Exposures at https://mothertobaby.org/fact-sheets/paternal-exposures-pregnancy/.
Oral bioavailability is nearly complete, at approximately 90%, and peak serum concentrations (Cmax) of, on average, 2.50 µg/mL are reached at 0.75 hours (Tmax). The AUC following an orally administered dose of 300mg was found to be approximately 11 µg•hr/mL. Systemic exposure from the administration of vaginal suppository formulations is 40-fold to 50-fold lower than that observed following parenteral administration and the Cmax observed following administration of vaginal cream formulations was 0.1% of that observed following parenteral administration.
来源:DrugBank
吸收、分配和排泄
消除途径
大约10%的克林霉素生物活性通过尿液排出，3.6%通过粪便排出，其余以无活性代谢物的形式排出。
Approximately 10% of clindamycin bioactivity is excreted in the urine and 3.6% in the feces, with the remainder excreted as inactive metabolites.
来源:DrugBank
吸收、分配和排泄
分布容积
克林霉素在体内广泛分布，包括进入骨骼，但不会分布到脑脊液中。分布容积估计在43-74升之间。
Clindamycin is widely distributed in the body, including into bone, but does not distribute into cerebrospinal fluid. The volume of distribution has been variably estimated between 43-74 L.
来源:DrugBank
吸收、分配和排泄
清除
克林霉素的血浆清除率估计为12.3-17.4升/小时，在肝硬化患者中降低，在贫血患者中有所改变。
The plasma clearance of clindamycin is estimated to be 12.3-17.4 L/h, and is reduced in patients with cirrhosis and altered in those with anemia.
Clindamycin is nearly completely absorbed following oral admin. Peak plasma concn of 2 to 3 ug/mL are attained within 1 hr after the ingestion of 150 mg. The presence of food in stomach does not reduce absorption. The half-life of the antibiotic is about 2.9 hr, and the modest accumulation of drug is thus expected if it is given at 6-hr intervals.
来源:Hazardous Substances Data Bank (HSDB)
文献信息
[EN] ISOTHIAZOLOQUINOLONES AND RELATED COMPOUNDS AS ANTI-INFECTIVE AGENTS<br/>[FR] ANTI-INFECTIEUX A BASE D'ISOTHIAZOLOQUINOLONES ET DE SELS CORRESPONDANTS
申请人：ACHILLION PHARMACEUTICALS INC
公开号：WO2005019228A1
公开（公告）日：2005-03-03
The invention provides compounds and salts of Formula (I) and Formula (II): which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula (I) and Formula (II). The variables A1, R2, R3, R5, R6, R7, A8 and R9 are defined herein. Certain compounds of Formula (I) and Formula (II) disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula (I) or Formula (II) and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula (I) or Formula (II) as the only active agent or may contain a combination of a compound of Formula (I) or Formula (II) and one or more other active agents. The invention also provides methods for treating microbial infections in animals.
The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.
这项发明提供了抗壁母细胞酸抗体及其抗生素结合物，以及使用它们的方法。
8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents
申请人：Bradbury J. Barton
公开号：US20060173026A1
公开（公告）日：2006-08-03
The invention provides compounds and salts of Formula I and Formula II:
which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables A
1
, A
8
, R
2
, R
3
, R
5
, R
6
, R
7
, and R
9
are defined herein.
Certain compounds of Formula I and Formula II disclosed herein are potent and selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of compounds of Formula I and/or Formula II and one or more other active agents. The invention also provides methods for treating microbial and protozoal infections in animals.
[EN] MODULATION OF IMMUNE RESPONSES BY ADMINISTRATION OF ROXITHROMYCIN OR ITS DERIVATIVE<br/>[FR] MODULATION DES RÉPONSES IMMUNES PAR ADMINISTRATION DE ROXITHROMYCINE OU DE SES DÉRIVÉS
申请人：Y S THERAPEUTICS CO LTD
公开号：WO2009023196A1
公开（公告）日：2009-02-19
Provided are compounds of formula (III) useful for modulation of immune responses, compositions comprising the compounds, and methods of use of such compositions for treating diseases or disorders involving an immune response. In certain embodiments, the compounds are useful for the treatment of diseases or disorders associated with transendothelial migration of T cells and activated T cells, and proinflammatory cytokine production from T cells and macrophages. Diseases or disorders that can be treated include arthritic and rheumatic disorders, such as rheumatoid arthritis.
8A,9-dihydro-4aH-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents
申请人：Bradbury J. Barton
公开号：US20060100215A1
公开（公告）日：2006-05-11
The invention provides compounds and salts of Formula I and Formula II:
which possess antimicrobial activity. The invention also provides novel synthetic intermediates useful in making compounds of Formula I and Formula II. The variables n, m, p, R
A
, R
B
, A
1
, R
2
, R
3
, R
5
, R
6
, R
7
, A
8
and R
9
are defined herein.
Certain compounds of Formula I and Formula II disclosed herein are potent and/or selective inhibitors of bacterial DNA synthesis and bacterial replication. The invention also provides antimicrobial compositions, including pharmaceutical compositions, containing one or more compounds of Formula I or Formula II and one or more carriers, excipients, or diluents. Such compositions may contain a compound of Formula I or Formula II as the only active agent or may contain a combination of a compound of Formula I or Formula II and one or more other active agents. The invention also provides methods for treating microbial infections in eukaryotes.
