Sparfloxacin (CAS 110871-86-8)

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. Zagam is no longer available in the United States.

Pharmacological properties

Sparfloxacin is about 37-45% bound to proteins in the blood.

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.

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. Sparfloxacin achieves excellent

penetration into human polymorphonuclear leukocytes in vitro.

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.

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%).

Medical uses

The compound is indicated for treating community-acquired lower respiratory tract infections

(acute sinusitis, exacerbations of chronic bronchitis caused by susceptible bacteria,

community-acquired pneumonia).

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 have not been reported

Mechanism of action

Sparfloxacin, like other quinolones and fluoroquinolones, are bactericidal medicine, 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.