Sparfloxacin

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Sparfloxacin
Sparfloxacin.svg
Sparfloxacin ball-and-stick.png
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 YesY
ATC code J01MA09
PubChem CID 60464
DrugBank DB01208
ChemSpider 54517 YesY
UNII Q90AGA787L YesY
KEGG D00590 YesY
ChEBI CHEBI:9212 YesY
ChEMBL CHEMBL850 YesY
Chemical data
Formula C19H22F2N4O3 
Mol. mass 392.41 g/mol
 YesY (what is this?)  (verify)

Sparfloxacin (spar FLOX a sin), trade names Spacin in Bangladesh, 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.

Pharmacological properties[edit]

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[edit]

  • 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[edit]

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[edit]

References[edit]

  1. ^ 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. PMC 2587028. PMID 18986285. 
  2. ^ Shimada, J.; Nogita, T.; Ishibashi, Y. (1993). "Clinical pharmacokinetics of sparfloxacin". Clinical pharmacokinetics 25 (5): 358–369. doi:10.2165/00003088-199325050-00002. PMID 8287631.  edit
  3. ^ 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
  4. ^ Johnson et al., 1992[full citation needed]
  5. ^ Nogita, T.; Ishibashi, Y. (1991). "The penetration of sparfloxacin into human plasma and skin tissues". The Journal of antimicrobial chemotherapy 28 (2): 313–314. doi:10.1093/jac/28.2.313. PMID 1663927.  edit
  6. ^ Garcia et al., 1992[clarification needed]
  7. ^ 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
  8. ^ 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. doi:10.1128/aac.37.4.633. PMC 187726. PMID 8388193.  edit
  9. ^ (p. II44)[clarification needed]
  10. ^ Ramsay and Obershkova, 1974[clarification needed]
  11. ^ Bowie et al., 1989[clarification needed]
  12. ^ Davey, 1989[clarification needed]
  13. ^ Wolfson and Hooper, 1991[clarification needed]
  14. ^ 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