Sparfloxacin

drugbox
IUPAC_name = 5-amino-1-cyclopropyl-7- [(3"R",5"S")3,5-dimethylpiperazin-
1-yl] -6,8-difluoro-4-oxo-quinoline-3-carboxylic acid

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CAS_number = 110871-86-8
ATC_prefix = J01
ATC_suffix = MA09
ATC_supplemental =
PubChem = 60464
DrugBank = APRD01231
C = 19 | H = 22 | F = 2 | N = 4 | O = 3
molecular_weight = 392.41 g/mol
bioavailability = 92%
protein_bound = 45%
metabolism = Hepatic glucuronidation
Cytochrome P450 system not involved
elimination_half-life = 16 to 30 hours
excretion = Fecal (50%) and renal (50%)
pregnancy_US = C
legal_US = Rx-only
routes_of_administration = Oral

What is it?

Sparfloxacin (spar FLOX a sin), trade names Zagam and Zagam Respipac, is a fluoroquinolone antibiotic used in the treatment of bacterial infections. Zagam is no longer available in the United States.

Pharmacological Properties:

Sparfloxacin is about 37- 45% bound to proteins in the blood(Shimada et at., 1993; Montay,1996).

*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 (Johnson et at., 1992).
*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 (Nogita and Ishibashi, 1991 ). Sparfloxacin achieves excellent penetration into human polymorphonuclear leukocytes in vitro (Garcia et at., 1992).
*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 (Wise and Honeybourne, 1996)Shimada et at. ( 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%) (Cochereau-Massin et at., 1993).

Adverse Drug Reactions:

*Sparfloxacin has a similar rate of adverse reactions as ciprofloxacin and other commonly used fluoroquinolones.
*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 4O0 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 400/200mg 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 (p.II44) have not been reported (Ram say and Obershkova, 1974; Bowie et at., 1989; Davey, 1989; Wolf son and Hooper, 1991; Rubinstein, 1996).

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.

Other Properties:

See fluoroquinolones