CIPROFLOXACIN: A SUCCESS STORY

Ciprofloxacin, has become a remarkable

success story in the pharmaceutical industry,
not only for being the first oral antimicrobial
drug with broad spectrum that can be used to
treat day-today as well as serious infections,
but also for its penetration into the
commercial market place.
Quinolones: Classification

First Generation Nalidixic acid

Oxolonic acid Third Generationb Sparfloxacin
Cinoxacin Gatifloxacin
Second Generation Ciprofloxacina Grepafloxacin
Norfloxacin
Lomefloxacin
Ofloxacin Fourth Generationc Trovafloxacin
Levofloxacin
Moxifloxacin
Gemifloxacin

a most potent vs. Pseudomonas

b more potent vs. S. pneumoniae and anaerobes than earlier compounds
c most potent vs. S. pneumoniae and anaerobes
Drugs 1999;58 Suppl 2:1-5
Ciprofloxacin: Chemical Structure

Ciprofloxacin is a 4-quinolone antibacterial durg

Effective against gram- O
positive and gram-
negative pathogens. F CO2H

N
N
Ciprofloxacin
HN

Effective against Confers potent

pseudomonas antimicrobial activity

Ref : Drugs 1988 (35: 373-447)

CIPROFLOXACIN: ANTIBACTERIAL SPECTRUM

Antibacterial spectrum ciprofloxacin has in vitro activity against a wide range of gram-negative, gram-
positive and atypical pathogens.
Gram-positive Gram-negative Atypical
S.epidermidis E.coli, L.pneumophila
S.pneumoniae H.influenzae M.pneumoniae
S.pyogenes K.pneumoniae C.trachomatis
N.gonorrhoeae
P.mirabilis
S.typhii
Serratia,
Shigella
M.catarrhalis
Pseudomonas

Others: Mycobacterium tuberculosis

Ciprofloxacin Highlights: Antimicrobial Spectrum

 Most active of the quinolones against Pseudomonas.

 More active than ofloxacin against Moraxella
catarrhalis and Chlamydia trachomatis.
 Greater or similar activity against Neisseria spp. than
Cefotaxime or Ceftazidime.
 S. typhi resistant strains are susceptible to
ciprofloxacin
 As active as ofloxacin against Staphylococci
1) Clinical Therapeutics 21(1) 1999:3-40
2) Ciprofloxacin, 10 years of Clinical Experience by Wilson et al.
Resistance To CIPROFLOXACIN

 In a survey of 67,000 isolates in the USA, most

enterobacteriaceae (99%), Staphylococci (98%) and
Pseudomonas aeruginosa (97%) were still susceptible to
ciprofloxacin
 On the basis of 1997-1999 test results of the SENTRY
antimicrobial surviellance results ,ciprofloxacin inhibited 100% of
H. influenzae and M. catarrhalis strains

Clinical infectious diseases 2000;31(suupl2):s16-s23

Ciprofloxacin : 10 years of clinical experience by wilson and Gruneberg
Ciprofloxacin: AUC/MIC Ratio

1800 1693
1600
1400
AUC/MIC Ratio

1200
1000 847 847 847
800
600 423 423 423 423
400
200
0

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AUC/MIC Ratio of Ciprofloxacin Comparing with Ofloxacin

1800
1600 Ciprofloxacin
1400
AUC/MIC Ratio

Ofloxacin
1200
1000
800
600
400
200
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HIGHLIGHTS OF CIPLOX (CIPROFLOXACIN)

 The most potent fluorinated quinolone

 Has a very broad spectrum of antibacterial activity
 Ensures rapid bactericidal activity at very low
concentrations
 Is rapidly distributed and adequate levels are achieved in
most tissues and body fluids with high intracellular
concentrations in the phagocytes
 Good bioavailability with an extended half-life of elimination
HIGHLIGHTS OF CIPLOX (CIPROFLOXACIN)

 Exhibits PAE against most organisms

 AUC/MIC ratios against various pathogens > 100
 Cmax/MIC ratios are in excess of 8-12
 Has proven efficacy in many types of systemic
infections as well as both chronic and acute infections
 Available as tablets as well as intravenous infusion
 Convenient twice-daily dosage
 Well tolerated by all patients
Why Ciplox once a day?

To enhance
patient
compliance
The Legend Blazes New
Trails…..
Introducing CIPLOX OD
CIPLOX OD 500 mg
CIPLOX OD 1000 mg
by using Gastro-retentive,Matrix Erosion
Diffusion or FED technology
Making of Ciplox OD : The Challenge

 OD ciprofloxacin was a
big challenge because of
a very narrow absorption
window of ciprofloxacin.
 Ciprofloxacin gets
absorbed only from the
stomach and the
duodenum which is
20-30 cms long.
Making of Ciplox-OD with FED technology
i.e. Float Erode Diffuse Technology

Ciplox OD floats
 Special components in
Ciplox OD come in contact
with acidic medium of the
stomach and propel the
tablet upwards.
 Tablet keeps floating on top
of gastric contents.
 Ensures availability of
ciprofloxacin in gastric
contents for the desired
period.
Making of Ciplox-OD with FED technology
i.e. Float Erode Diffuse Technology

Ciplox OD erodes
 Ciprofloxacin in
Ciplox OD is
embedded in
polymer chains.
 Acidic medium of
stomach dissolves
polymers allowing
ciprofloxacin
release in a
controlled manner.
Making of Ciplox-OD with FED technology
i.e. Float Erode Diffuse Technology

Ciplox OD diffuses
Ciprofloxacin gets
dissolved in acidic
medium, diffusing out
in a controlled
manner.
PHARMACOKINETIC COMPARISON OF
CIPROFLOXACIN 1000MG OD AND 500MG BID
10000
Mean Concentration (ng/mL)

A Conclusion
T
1000 Ciprofloxacin 1000 mg OD
tablet is expected to provide
similar efficacy as the
conventional tablet 500 mg
100
0 5 10 15 20 25
T im e ( h o u r s )

Parameters Cmax AUC0-t AUC>MIC 1 mcg/mL

T/A Ratio 112.63 105.32 210.24

T=Ciprofloxacin OD Tablets 1000 mg; B.No. VD (1004)50;
Ranbaxy Research Laboratories
A=Cipro 500 mg Tablets; B.No. 9LFT; Bayer
Ciplox-OD : AECB

 No. of patients
65
 Treatment
Ciplox 1000 mg tablets once a day for 10 days
 Clinical efficacy (n=65)
97%
 Bacteriological efficacy (n=56)
(organisms:S.pneumoniae,H.influenzae,S.aureus,
 Pseudomonas)
 100%
 Safety
No adverse events were reported
Data on file
Ciplox-OD: Skin and skin structure infections

No of patients
27
Treatment
Ciplox 1000 mg tablet once daily for 10 days.
Clinical cure or improvement 96%
Bacteriological Eradication 90.5%
(Organisms eradicated:S.aureus,S.pyogenes,klebsiella)
Safety
No serious adverse events reported
Conclusion
Ciplox-OD tablets are highly effective and safe in the treatment of
skin and skin structure infections.
Ref.: Data on file
Ciplox-OD :- Uncomplicated Urinary Tract
Infection
No of patients
24
Treatment
Patients received treatment with Ciplox 500mg tablet once a day or conventional
release ciprofloxacin 250mg tablet twice a day for 3 days.
Outcome Ciprofloxacin Ciprofloxacin
500mg OD 250mg bid
(n=12) (n=12)
Clinical cure 100 % 91.7 %
Bacterial Eradication(E.coli,
Klebsiella,Pseudomonas) 100 % 85 %
Safety
No adverse events were reported.
Ref : data on file.
Ciplox-OD :- Complicated Urinary Tract Infection

No of patients
21
Treatment
Patients received treatment with Ciplox 1000mg tablet once a day or
conventional release ciprofloxacin 500mg tablet twice a day for14 days.
Outcome Ciprofloxacin Ciprofloxacin
1000mg OD 500mg bid
(n=10) (n=11)
Clinical cure 75 % 100 %
Bacterial Eradication 100 % 100 %
Safety
No adverse events were reported.
Ref : data on file.
Ciplox-OD : Safety and Tolerability

 Ciplox-OD (as 500 mg od or 1000 mg od) is safe

and well tolerated
 Adverse effects (Nausea, gastritis) were 4.3%
similar with that observed with conventional tablet
 No discontinuation of therapy observed with
Ciplox-OD
Data on file
Ciplox-OD: Indications
Ciplox -OD is indicated for the treatment of the following
infections caused by susceptible microorganisms.
 Acute sinusitis
 Lower respiratory infections including pneumonia and acute
exacerbations of chronic bronchitis.
 Chronic bacterial prostatitis
 Complicated intra-abdominal infections (used in combination
with metronidazole)
 Skin and skin structure infections
 Bone and joint infections
 Infectious diarrhoea
 Typhoid fever
Ciplox-OD: Dosage and administration
Directions for use of Ciplox-OD 500 mg and Ciplox-OD 1000 mg tablets:
Do not cut, crush of chew the tablets. The tablets must be taken after
meals and swallowed whole.

Infections Type of Severity Daily Dose Frequency Usual

of adminis- Duration †

tration of OD
Acute Mild/Moderate 1000 mg q 24 h 10 days
Sinusitis
Lower Mild/Moderate 1000 mg q 24 h 7 -14 days
Respiratory Severe/ 1500 mg q 24 h 7 -14 days
Tract Complicated
Ciplox-OD: Dosage and administration (Contd.)

Infections Type of Severity Daily Dose Frequency Usual

of adminis- Duration †

tration of OD
Urinary Tract Acute 500 mg q 24 h 3 days
Uncomplicated
Mild/Moderate 500 mg q 24 h 7 -14 days
Severe/Compli- 1000 mg q 24 h 7 -14 days
cated
Chronic Bacte- Mild/Moderate 1000 mg q 24 h 28 days
rial Prostatitis
Intra-abdominal* Complicated 1000 mg q 24 h 7 -14 days
Skin and skin Mild/Moderate 1000 mg q 24 h 7 -14 days
structure Severe/Compli- 1500 mg q 24 h 7 -14 days
cated
Ciplox-OD: Dosage and administration (Contd.)

Infections Type of Severity Daily Dose Frequency Usual

of adminis- Duration †
tration of OD
Bone and joint Mild/Moderate 1000 mg q 24 h >4-6
Infectious Severe/Complicated 1500 mg q 24 h > 4 - 6 weeks
diarrhoea Mild/Moderate/ 1000 mg q 24 h 5 -7 days
Typhoid fever severe
Mild/Moderate 1000 mg q 24 h 10 days
* used in conjunction with metronidazole
† generally ciprofloxacin should be continued for at least 2 days after the
signs and symptoms of infection have disappeared
Ciplox-OD Highlights

 Novel once daily formulation for the first time in the world
 Innovative technology - Gastro-retentive ,Matrix erosion
diffusion or FED technology
 AUC/MIC ratios and Cmax/MIC ratios higher for various
organisms. Thereby exhibits excellent bacterial power
 More bactericidal then conventional ciprofloxacin tablet
 Excellent efficacy in respiratory tract, skin and skin
structure and urinary tract infections
 Safe and well tolerated
 Enhance patient compliance