CIPROFLOXACIN: A SUCCESS STORY

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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.

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Quinolones Classification

• First Generation Nalidixic acid Oxolonic
  acid Cinoxacin
• Second Generation Ciprofloxacina
• Norfloxacin Lomefloxacin Ofloxacin Levofloxaci
  n

Third Generationb Sparfloxacin Gatifloxacin Grep
afloxacin Fourth Generationc Trovafloxacin Moxif
loxacin 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 199958 Suppl 21-5
3
Ciprofloxacin Chemical Structure

• Ciprofloxacin is a 4-quinolone antibacterial durg

Effective against gram-positive and gram-negative
pathogens.
O
F
CO2H
Effective against pseudomonas
N
N
Ciprofloxacin
Confers potent antimicrobial activity
HN
Ref Drugs 1988 (35 373-447)
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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

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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) 19993-40
• 2) Ciprofloxacin, 10 years of Clinical Experience
  by Wilson et al.

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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 200031(suupl2)s16-s
  23
• Ciprofloxacin 10 years of clinical experience
  by wilson and Gruneberg

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Ciprofloxacin AUC/MIC Ratio
AUC/MIC Ratio
Organisms
Pharmacotherapy 2000 20(4) 417-428
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AUC/MIC Ratio of Ciprofloxacin Comparing with
Ofloxacin
AUC/MIC Ratio
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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

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HIGHLIGHTS OF CIPLOX(CIPROFLOXACIN)

• Exhibits PAE against most organisms
• AUC/MIC ratios against various pathogens gt 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

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Why Ciplox once a day?

• To enhance patient compliance

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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

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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 is20-30 cms long.

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Making of Ciplox-OD with FED technologyi.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.

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Making of Ciplox-OD with FED technologyi.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.

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Making of Ciplox-OD with FED technologyi.e.
Float Erode Diffuse Technology

• Ciplox OD diffuses
• Ciprofloxacin gets dissolved in acidic medium,
  diffusing out in a controlled manner.

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PHARMACOKINETIC COMPARISON OF CIPROFLOXACIN
1000MG OD AND 500MG BID
Conclusion Ciprofloxacin 1000 mg OD tablet is
expected to provide similar efficacy as the
conventional tablet 500 mg
Mean Concentration (ng/mL)

• Parameters Cmax AUC0-t AUCgtMIC 1 mcg/mL
• T/A Ratio 112.63 105.32 210.24
• TCiprofloxacin OD Tablets 1000 mg B.No. VD
  (1004)50Ranbaxy Research Laboratories
• ACipro 500 mg Tablets B.No. 9LFT Bayer

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Ciplox-OD AECB

• No. of patients65
• TreatmentCiplox 1000 mg tablets once a day for
  10 days
• Clinical efficacy (n65)97
• Bacteriological efficacy (n56)(organismsS.pneum
  oniae,H.influenzae,S.aureus,
• Pseudomonas)
• 100
• SafetyNo adverse events were reported
• Data on file

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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 eradicatedS.aureus,S.pyogenes,klebsiel
  la)
• 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

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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 (n12) (n12)
• Clinical cure 100 91.7
• Bacterial Eradication(E.coli,
• Klebsiella,Pseudomonas) 100 85
• Safety
• No adverse events were reported.
• Ref data on file.

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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 (n10) (n11)
• Clinical cure 75 100
• Bacterial Eradication 100 100
• Safety
• No adverse events were reported.
• Ref data on file.

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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

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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

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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 daysSinusitis Lower Mild/Moderate 1000
mg q 24 h 7 -14 daysRespiratory Severe/ 1500
mg q 24 h 7 -14 daysTract Complicated
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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
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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 100
0 mg q 24 h gt 4 - 6 Infectious Severe/Complicated
1500 mg q 24 h gt 4 - 6 weeks diarrhoea Mild/Moder
ate/ 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
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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