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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/05 14:27:25」(JST)
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Sparfloxacin
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| Systematic (IUPAC) name |
5-amino-1-cyclopropyl-7-[(3R,5S)3,5-dimethylpiperazin-
1-yl]-6,8-difluoro-4-oxo-quinoline-3-carboxylic acid |
| Clinical data |
| AHFS/Drugs.com |
Micromedex Detailed Consumer Information |
| MedlinePlus |
a600002 |
| Pregnancy cat. |
C (US) |
| Legal status |
℞-only (US) |
| Routes |
Oral |
| Pharmacokinetic data |
| Bioavailability |
92% |
| Protein binding |
45% |
| Metabolism |
Hepatic glucuronidation
Cytochrome P450 system not involved |
| Half-life |
16 to 30 hours |
| Excretion |
Fecal (50%) and renal (50%) |
| Identifiers |
| CAS number |
110871-86-8 Y |
| ATC code |
J01MA09 |
| PubChem |
CID 60464 |
| DrugBank |
DB01208 |
| ChemSpider |
54517 Y |
| UNII |
Q90AGA787L Y |
| KEGG |
D00590 Y |
| ChEBI |
CHEBI:9212 Y |
| ChEMBL |
CHEMBL850 Y |
| Chemical data |
| Formula |
C19H22F2N4O3 |
| Mol. mass |
392.41 g/mol |
SMILES
- C[C@@H]1CN(C[C@@H](N1)C)c2c(c(c3c(c2F)n(cc(c3=O)C(=O)O)C4CC4)N)F
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InChI
-
InChI=1S/C19H22F2N4O3/c1-8-5-24(6-9(2)23-8)17-13(20)15(22)12-16(14(17)21)25(10-3-4-10)7-11(18(12)26)19(27)28/h7-10,23H,3-6,22H2,1-2H3,(H,27,28)/t8-,9+ Y
Key:DZZWHBIBMUVIIW-DTORHVGOSA-N Y
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Y (what is this?) (verify)
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Sparfloxacin (spar FLOX a sin), trade names Zagam and Zagam Respipac, is a fluoroquinolone antibiotic used in the treatment of bacterial infections. It has a controversial safety profile.[1] Zagam is no longer available in the United States.
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Contents
- 1 Pharmacological properties
- 2 Adverse drug reactions
- 3 Mechanism of action
- 4 See also
- 5 References
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Pharmacological properties
Sparfloxacin is about 37- 45% bound to proteins in the blood.[2][3]
- Sparfloxacin achieves a high degree of penetration into most tissues, except for the central nervous system.
- Following a single 400 mg oral dose of sparfloxacin, the mean peak concentration in cantharides-induced inflammatory fluid is 1.3 lA-g per ml after a mean duration of 5 h post-dose. Thus(overall sparfloxacin penetration into inflammatory fluid is 117% and the mean elimination half-life from this fluid is 19.7 h.[4]
- Skin penetration of sparfloxacin is good with skin:plasma ratios of 1.00 at 4 h (time of peak plasma concentration) and 1.39 at 5 h. Following single oral doses of 100 or 200 mg, concentrations in skin of 0.56 and 0.82-1.31 lA-g per g, respectively, can be expected.[5] Sparfloxacin achieves excellent penetration into human polymorphonuclear leukocytes in vitro.[6]
- Sparfloxacin achieves high concentrations in respiratory and sinus tissues. Following an oral loading dose of 400 mg followed by 200 mg daily, mean concentrations of sparfloxacin (2.5 to 5 h after dosing) in bronchial mucosa, epithelial lining fluid and alveolar macrophages are 4.4 µg/g, 15.0 µg/ml and 53.7 µg/g, respectively. The mean sparfloxacin concentration in maxillary sinus mucosa, 2-5 h after a single 400 mg dose, is 5.8 µg/g.[7]
Shimada et al. ( 1993) has summarized many of the studies published in Japanese regarding the tissue distribution of sparfloxacin. (high concentrations are achieved in sputum, pleural fluid, skin, lung, prostate, gynecological tissues, breast milk and otolaryngological tissues. *Salivary concentrations are 66-70% of plasma levels, while CSF penetration appears to be somewhat limited with CSF:plasma concentration ratios of only 0.25-0.35.
- Sparfloxacin achieves concentrations in bile and gallbladder of 7.1- to 83-fold the concurrent serum levels.
In rabbits, sparfloxacin achieves very good penetration into the ocular vitreous (54%), cornea (76%) and lens (36%).[8]
Adverse drug reactions
See also: Quinolone#Adverse effects
- In a review of 2081 adult patients participating in a Phase III clinical trial of sparfloxacin in community-acquired, lower respiratory tract infections, sparfloxacin (200- or 400 mg loading dose then 100 or 200 mg daily; i.e. 200/100 mg and 400/200 mg) had a similar incidence of adverse events as the comparator agents (Rubinstein, 1996). The overall rates of drug-related adverse reactions for sparfloxacin 400/200 mg versus comparators and 200/100 mg versus the comparator (amoxycillin/clavulanic acid) were 13.7 versus 17.7%, and 9.5 versus 13.2%, respectively. However, many of these reported reactions were very minor; discontinua- tion of the antibacterial agent because of drug-related adverse reactions occurred in 1.6 versus 1.6%, and 1) versus 1.1%, respectively. Adverse reactions affecting the nervous system were reported in 5.7% of the sparfloxacin group, with insomnia and other sleep disorders the most common events.
- Phototoxicity was noted in 2.0% of sparfloxacin recipients, with the average delay in onset being 6.3 :t 4.5 days (range 1–14 days) after commencing sparfloxacin. Mostly this consisted of erythema on the face and hands which lasted an average of 6.4 :t 4.2 days. The incidence of phototoxicity associated with sparfloxacin appears to be higher than that observed with ciprofloxacin and ofloxacin but less than that reported for fleroxacin, pefloxacin, enoxacin and nalidixic acid.
- Most importantly, features of the hemolytic-uremic syndrome such as that associated with temafloxacin[9] have not been reported.[10][11][12][13][14]
Mechanism of action
Sparfloxacin, like other quinolones and fluoroquinolones, are bactericidal drugs, actively killing bacteria. Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Quinolones can enter cells easily and therefore are often used to treat intracellular pathogens such as Legionella pneumophila and Mycoplasma pneumoniae. For many gram-negative bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV.
See also
- Fluoroquinolones
- Fluoroquinolone toxicity
References
- ^ Psaty, BM. (Dec 2008). "Clinical trial design and selected drug safety issues for antibiotics used to treat community-acquired pneumonia.". Clin Infect Dis 47 Suppl 3: S176-9. doi:10.1086/591400. PMID 18986285.
- ^ Shimada, J.; Nogita, T.; Ishibashi, Y. (1993). "Clinical pharmacokinetics of sparfloxacin". Clinical pharmacokinetics 25 (5): 358–369. PMID 8287631. edit
- ^ Montay, G. (1996). "Pharmacokinetics of sparfloxacin in healthy volunteers and patients: A review". The Journal of antimicrobial chemotherapy 37 Suppl A: 27–39. PMID 8737123. edit
- ^ Johnsonrffg4rfgerfgr3rf4rfgrferfg4rt et al., 1992[clarification needed]
- ^ Nogita, T.; Ishibashi, Y. (1991). "The penetration of sparfloxacin into human plasma and skin tissues". The Journal of antimicrobial chemotherapy 28 (2): 313–314. PMID 1663927. edit
- ^ Garcia et al., 1992[clarification needed]
- ^ Wise, R.; Honeybourne, D. (1996). "A review of the penetration of sparfloxacin into the lower respiratory tract and sinuses". The Journal of antimicrobial chemotherapy 37 Suppl A: 57–63. PMID 8737125. edit
- ^ Cochereau-Massin, I.; Bauchet, J.; Marrakchi-Benjaafar, S.; Saleh-Mghir, A.; Faurisson, F.; Vallois, J. M.; Vallee, E.; Pocidalo, J. J. (1993). "Efficacy and ocular penetration of sparfloxacin in experimental streptococcal endophthalmitis". Antimicrobial agents and chemotherapy 37 (4): 633–636. PMC 187726. PMID 8388193. //www.ncbi.nlm.nih.gov/pmc/articles/PMC187726/. edit
- ^ (p. II44)[clarification needed]
- ^ Ramsay and Obershkova, 1974[clarification needed]
- ^ Bowie et al., 1989[clarification needed]
- ^ Davey, 1989[clarification needed]
- ^ Wolfson and Hooper, 1991[clarification needed]
- ^ Rubinstein, E. (1996). "Safety profile of sparfloxacin in the treatment of respiratory tract infections". The Journal of antimicrobial chemotherapy 37 Suppl A: 145–160. PMID 8737134. edit
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Antibacterials: nucleic acid inhibitors (J01E, J01M)
|
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Antifolates
(inhibits
purine metabolism,
thereby inhibiting
DNA and RNA synthesis) |
| DHFR inhibitor |
- 2,4-Diaminopyrimidine
- Trimethoprim#
- Brodimoprim
- Tetroxoprim
- Iclaprim†
|
|
Sulfonamides
(DHPS inhibitor) |
Short-
acting |
- Sulfaisodimidine
- Sulfamethizole
- Sulfadimidine
- Sulfapyridine
- Sulfafurazole
- Sulfanilamide
- Sulfathiazole
- Sulfathiourea
|
|
Intermediate-
acting |
- Sulfamethoxazole
- Sulfadiazine#
- Sulfamoxole
|
|
Long-
acting |
- Sulfadimethoxine
- Sulfadoxine
- Sulfalene
- Sulfametomidine
- Sulfametoxydiazine
- Sulfamethoxypyridazine
- Sulfaperin
- Sulfamerazine
- Sulfaphenazole
- Sulfamazone
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|
|
| Other/ungrouped |
- sulfanilamide
- Sulfacetamide
- Sulfametrole
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|
| Combinations |
- Trimethoprim/sulfamethoxazole#
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|
|
Topoisomerase
inhibitors/
quinolones/
(inhibits
DNA replication) |
| 1st g. |
- Cinoxacin‡
- Flumequine
- Nalidixic acid
- Oxolinic acid
- Pipemidic acid
- Piromidic acid
- Rosoxacin
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|
Fluoro-
quinolones |
| 2nd g. |
- Ciprofloxacin#
- Enoxacin‡
- Fleroxacin‡
- Lomefloxacin
- Nadifloxacin
- Ofloxacin
- Norfloxacin
- Pefloxacin
- Rufloxacin
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|
| 3rd g. |
- Balofloxacin
- Grepafloxacin‡
- Levofloxacin
- Pazufloxacin
- Sparfloxacin‡
- Temafloxacin‡
- Tosufloxacin
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|
| 4th g. |
- Besifloxacin
- Clinafloxacin†
- Garenoxacin
- Gemifloxacin
- Moxifloxacin
- Gatifloxacin‡
- Sitafloxacin
- Trovafloxacin‡/Alatrofloxacin‡
- Prulifloxacin
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|
| Vet. |
- Danofloxacin
- Difloxacin
- Enrofloxacin
- Ibafloxacin
- Marbofloxacin
- Orbifloxacin
- Pradofloxacin
- Sarafloxacin
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|
| Related (DG) |
- Aminocoumarins: Novobiocin
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|
|
|
Anaerobic DNA
inhibitors |
| Nitro- imidazole derivatives |
- Metronidazole#
- Tinidazole
- Ornidazole
|
|
| Nitrofuran derivatives |
- Nitrofurantoin#
- Furazolidone‡
- Nifurtoinol
|
|
|
| RNA synthesis |
Rifamycins/
RNA polymerase |
- Rifampicin#
- Rifabutin
- Rifapentine
- Rifaximin
|
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
|
|
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gr+f/gr+a(t)/gr-p(c)/gr-o
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UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
English Journal
- Role of mixed ion channel effects in the cardiovascular safety assessment of the novel anti-MRSA fluoroquinolone JNJ-Q2.
- Eichenbaum G, Pugsley M, Gallacher Dj, Towart R, McIntyre G, Shukla U, Davenport J, Lu H, Rohrbacher J, Hillsamer V.SourceJanssen Research & Development, LLC., a division of Janssen Pharmaceutical Companies of Johnson & Johnson, Drug Safety Sciences, Raritan, NJ, USA Janssen Research & Development, a division of Janssen Pharmaceutica N.V., Beerse, Belgium Furiex Pharmaceuticals, Blue Bell, PA, USA Furiex Pharmaceuticals, Richmond, VA, USA.
- British journal of pharmacology.Br J Pharmacol.2012 Jul;166(5):1694-707. doi: 10.1111/j.1476-5381.2012.01874.x.
- BACKGROUND AND PURPOSE: JNJ-Q2, a novel broad-spectrum fluoroquinolone with anti-methicillin-resistant Staphylococcus aureus activity, was evaluated in a comprehensive set of non-clinical and clinical cardiovascular safety studies. The effect of JNJ-Q2 on different cardiovascular parameters was comp
- PMID 22289150
- Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates.
- Wen D, Liu A, Chen F, Yang J, Dai R.SourceSouth China University of Technology, Guangzhou, 510641, China; Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
- Journal of applied toxicology : JAT.J Appl Toxicol.2012 Jun 29. doi: 10.1002/jat.2755. [Epub ahead of print]
- Drug-induced QT prolongation usually leads to torsade de pointes (TdP), thus for drugs in the early phase of development this risk should be evaluated. In the present study, we demonstrated a visualized transgenic zebrafish as an in vivo high-throughput model to assay the risk of drug-induced QT pro
- PMID 22744888
Japanese Journal
- 前立腺針生検後の発熱性感染症予防における抗菌薬投与の検討
- 小林 聡,牧 知子,小林 武 [他],濵口 益光,吉川 正博,坂本 直孝,井口 厚司
- 泌尿器科紀要 = Acta urologica Japonica 60(5), 227-230, 2014-05
- … SPFX (sparfloxacin) 400 mg (January 2007 to March 2010) and LVFX (levofloxacin) 500 mg (April 2010, onward) were administered prophylactically in 1, 034 patients undergoing transrectal or transperineal prostate biopsy. … Sparfloxacin. …
- NAID 120005439522
- Long-Evansラットを用いたLomefloxacin，SparfloxacinおよびPirfenidoneの薬剤性光線過敏症リスクの評価 －組織移行性の検討－
- 三輪 恵子,足立 民子,佐藤 優子,佐藤 寛子,竹川 晃司,杉山 明男
- 日本毒性学会学術年会 39.1(0), P-217, 2012
- … 創薬の過程において薬剤性光線過敏症のリスク評価が重要になっている．今回，ヒトで光線過敏症が報告されているLomefloxacin（LMFX，50，100，200 mg/kg），Sparfloxacin（SPFX，50，100，200 mg/kg）およびPirfenidone（PFD，160，320，750 mg/kg）をLong-Evans（LE）ラット（雌）に単回投与し，各化合物のTmaxに近い時点で背部皮膚および眼にUVAを30分間照射（10J/cm2）して4日後まで観察するとともに，血漿，眼球および背部皮膚中濃度をLC/MS/MS法 …
- NAID 130005008824
Related Links
- Sparfloxacin [SPFX] スパルフロキサシン, 持続性ニューキノロン 1. 商品名 先発品 スパラ錠100mg 【大日本住友製薬】 2. 日本における発売年 1993（平成5）年 3. 特長 グラム陽・陰性菌やクラミジア等に対し，広い抗菌スペクトルを 有す． ...
- Sparfloxacinとは？goo Wikipedia (ウィキペディア) 。出典：Wikipedia（ウィキペディア）フリー百科事典。 Sparfloxacinとは - goo Wikipedia (ウィキペディア) gooトップ サイトマップ スタートページに設定 RSS ヘルプ メニューへスキップ ...
Related Pictures
★リンクテーブル★
[★]
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