Amifloxacin - Fluroquinolone antibiotic- Investigational Drugs
Drug Name:Amifloxacin - Fluroquinolone antibiotic- Investigational Drugs
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Pharmacology/ Pharmacokinetics
Indication:
Urinary tract infection
Summary-
Amifloxacin is fluroquinolone antibiotic with activity and pharmacokinetics similar to
other commercially available quinolones. Becuase it is primarily renally eliminated,
it may be efective for the treatment of urinary tract inections. Overall it appears to be
well tolerated with side effect being GI in nature.
At this time, amifloxacin research has ended.
Adverse Reaction:
Side effects-
In clinical trials the adverse effects seen with amifloxacin were mild and self limited.
In the multiple dose study four patients required discontinuation of therpy due to
amifloxacin, one developed pruritus and three experienced a 5-to 8 fold increase in
serum ALT.( above upper limits ) that was asymptomatic and resolved
spontaneously once the drug was discontinued.
The primary adverse effects were nausea ( 15%) abdominal pain (8.3%)
dyspepsia (6.7%) headache 8.3%) insomnia (3.3%) tinnitus (3.3%) and
pruritus (5%). The renal (asymptomatic crsrystaluria) and hepatic adverse
effects were seen in subjects receiving > 1200mg daily . Doses <1200mg daily
were well tolerated
Pharmacology/ Pharmacokinetics:
Pharmacology-
Amifloxacin is a fluorinated quinolone -carboxylic acid that is structurally related to
nalidixic acid (NegGram) and cloxacin (Cinobac). It is a broad spectrum of activity
against many gram-positive and gram-negative organisms including Escheria coli,
Klebsiella pneumomoniae .Proteus vulgaris, citrobacter freundi, Pseudomonas
aeruginosa and Serratia marccescens
Becuase of its high degree of renal excretion, it may be effective for treatment of
urinary tract infections.
Pharmacokinetics-
The pharmacokinetic parameters of multiple oral dosing of amifloxacin were evaluated
in 48 men randomized to receive amifloxacin every 12 hours( 200,400, or 600mg) or
8 hours( 400, 600,800mg) orally for 10 days.
Amifloxacin was rapidly absorbed with Tmax of 0.98 hours. Steady state concentrations
in the urine were > 100mcg/ml for all doses except for 200mg every 12 hours regimen
( where the concentration was > 40mcg/ml). The half life ranged from 4.25 to 5.78 hours,
and the renal clearance ranged from 128 to 73 ml/hr/kg with the 200mg every 12 hour
and 800mg every 8 hours regimen respy.
The major route of elimination was renal with ~ 54% of the administered dose excreted
in the urine. Amifloxacin exhibited concentration -dependent , pharmacokinetics.
Pharmacokinetic parameters were comparable to those of other quinolones.
A single dose of amifloxacin 200mg was evaluated in 10 elderly subjects(aged 65
to 79 years). The time to maximum concentration for women was 1.6 hrs , the half-life was
5.37 hrs for men and 4.47 hrs for women and 42% was excreted renally.
Dose adjustments in elderly is probably not necessary.
Clinical trials-
The in vitro activity of amifloxacin was compared with that of ciprofloxacin(Cipro) and
ofloxacin ( Floxin) against 500 isolates of gram positive and gram -negative bacteria.
Overall, amifloxacin had high invitro activity against a wide range of organisms
especially Enterobacteriaceae
In another trial the invitro activity of amifloxacin against Streptococcus saprophytus
and E Coli was compared with that of other antibiotics use for the treatment of acute
urinary tract infections. The drugs evaluated included amifloxacin, gentamicin
(Garamycin), amoxicillin (Amoxil) cephalexin (Keflex) trimethoprim (TMP, Tiempex)
trimethoprim-sulfamethoxazole (TMP-SMZ eg Septra) and conoxcin ( Cinobac)
Overall the isolates were susceptible to TMP-SMZ , TMP and amifloxacin than to
other drugs tested.
The invitro activity of seven different quinolone antibiotics ( ciprofloxacin, ofloxacin ,
amifloxacin, enoxacin , norfloxacin and two investigational agents ) against
115bstrains of MRSA was evaluated, All the agents were effectively bactericidal.
In vitro trials with amifloxacin that have published to are limited. In one trial, the
safety and efficacy of amifloxacin was compared with that of SMZ/TMP for the
treatment of uncomplicated urinary tract infection in women (n=153) with signs and
symptoms of a UTI and bacteria in urine. Patients received amifloxacin 200mg
every 12 hrs(n-52) or 400mg for 12 hrs(n=54) or TMP 160mg /SMZ 800mg every
12hrs (n=47) for 10 days.
The outcome was defined as bacterologic cure , failure or superinfection , and
clinical cure or improvement. There was no significant difference in bacterologic
cure rate at between the two drugs. All evaluable patients showed clinical
improvement or cure at 5 to 9 days visit.
Persistent cure was seen in almost all cases at the 4 to 6 week follow-up visit.
