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D O Shah - One of the best experts on this subject based on the ideXlab platform.
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tailored Gatifloxacin pluronic f 68 loaded contact lens addressing the issue of transmittance and swelling
International Journal of Pharmaceutics, 2020Co-Authors: Furqan A Maulvi, S. A. Shah, Riya J Parmar, Ankita R Desai, Ditixa M Desai, Manish Shukla, Ketan M Ranch, D O ShahAbstract:Abstract Loading of Gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve Gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized Gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and Gatifloxacin loading capacity as well as sustained drug delivery. Optimization of Gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of Gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and Gatifloxacin loading capacity of 92.56 μg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct Gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo Gatifloxacin release data for rabbit tear fluid showed sustained release with a high Gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize Gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.
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plackett burman design for screening of critical variables and their effects on the optical transparency and swelling of Gatifloxacin pluronic loaded contact lens
International Journal of Pharmaceutics, 2019Co-Authors: Furqan A Maulvi, S. A. Shah, Riya J Parmar, Ankita R Desai, Manish Shukla, Ketan M Ranch, Ditixa T Desai, Susan Sandeman, D O ShahAbstract:Abstract The optical and swelling properties of Gatifloxacin-loaded contact lens decrease owing to the precipitation of Gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the Gatifloxacin precipitates and not limited to sustain the release of Gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of Gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X 1 , %w/v), the concentration of Pluronic F68 in the packaging solution (X 2, %w/v), the concentration of Gatifloxacin incorporated in the monomer solution (X 3, %w/v), the concentration of Gatifloxacin incorporated in the packaging solution during autoclave (X 4 , %w/v), the concentration of Gatifloxacin incorporated in the packaging solution during extraction (X 5 , %w/v), the time (stabilization time) after the addition of Gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X 6 , h), the pH of the packaging solution (X 7 ), the temperature of the extracted solution (X 8 , °C), and the curing time for fabricating the contact lens (X 9 , min). The Gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y 1 , %), optical transmittances after 7 days of sterilization (Y 2 , %) and swelling percentages after 7 days of sterilization (Y 3 , %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y 1 , Y 2 , and Y 3 , respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X 1 ) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X 2 ) improved them through micelle formation. The other variables (X 3 to X 9 ) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of Gatifloxacin-loaded contact lens.
Dennis M Grasela - One of the best experts on this subject based on the ideXlab platform.
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clinical pharmacology of Gatifloxacin a new fluoroquinolone
Clinical Infectious Diseases, 2000Co-Authors: Dennis M GraselaAbstract:Gatifloxacin is an advanced-generation, 8-methoxy fluoroquinolone that is active against a broad spectrum of pathogens, including antibiotic-resistant Streptococcus pneumoniae. The drug has high oral bioavailability (96%), and, therefore, oral and intravenous formulations are bioequivalent and interchangeable. Gatifloxacin has a large volume of distribution (∼1.8 L/kg), low protein binding (∼20%), and broad tissue distribution and is primarily excreted unchanged in the urine (>80%). Gatifloxacin can be administered without dose modification in patients with hepatic impairment, in women, and in the elderly. In vitro experiments and clinical studies indicate that Gatifloxacin does not interact with drugs metabolized by the cytochrome P450 enzyme family. At therapeutically relevant doses, Gatifloxacin's pharmaco-dynamically linked parameters (the ratio of maximum serum concentration to minimum inhibitory concentration and the ratio of the area under the curve to minimum inhibitory concentration) are similar to or better than those of other fluoroquinolones. Clinical studies show that Gatifloxacin has limited potential to prolong the QT interval on the electrocardiogram and lacks the potential to cause photosensitivity reactions, to alter oral glucose tolerance, or to cause crystalluria.
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effect of multiple dose Gatifloxacin or ciprofloxacin on glucose homeostasis and insulin production in patients with noninsulin dependent diabetes mellitus maintained with diet and exercise
Pharmacotherapy, 2000Co-Authors: Diptee A Gajjar, Frank Lacreta, Georgia Kollia, Randall R Stolz, Sheldon Berger, William B Smith, Mary Swingle, Dennis M GraselaAbstract:Study Objectives. To compare the effects of Gatifloxacin and ciprofloxacin on glucose homeostasis, including glucose tolerance test (GTT), pancreatic β-cell function, and insulin production and secretion in patients with noninsulin-dependent (type 2) diabetes mellitus (NIDDM) maintained with diet and exercise; and to evaluate the pharmacokinetics, safety, and tolerability of Gatifloxacin. Design. Randomized, double-blind, placebo-controlled, multiple-dose study. Setting. GFI Pharmaceutical Services, Inc., Evansville, Indiana; Chicago Center for Clinical Research, Chicago, Illinois; and New Orleans Center for Clinical Research, New Orleans, Louisiana, USA. Patients. Forty-eight men and women with NIDDM. Interventions. Patients were assigned sequentially at enrollment to receive Gatifloxacin 400 mg/day orally, ciprofloxacin 500 mg twice/day orally, or placebo for 10 days. Oral GTTs were performed on specific days throughout the study, as well as measurements of serum glucose, serum insulin, and C-peptide levels. Physical examinations, electrocardiograms, spirometry, and clinical laboratory tests were performed before dosing and on selected dosing days. Measurements and Main Results. Gatifloxacin had no significant effect on glucose tolerance and pancreatic β-cell function, as shown by oral GTT results and insulin and C-peptide levels. Fasting glucose levels 0–6 hours after Gatifloxacin administration on days 1 and 10 showed a downward trend, but it was not significant compared with placebo; results were similar with ciprofloxacin. Gatifloxacin also lacked a long-term effect on fasting insulin levels, but this was not shown for a short-term effect, suggesting a modest, transient effect on insulin release. On the other hand, ciprofloxacin had no short-term effect but produced a more sustained effect on insulin release and production. The pharmacokinetics of Gatifloxacin in patients with NIDDM were similar to those in healthy subjects. Overall, subjects tolerated treatment well. All reported drug-related adverse events were mild to moderate in intensity. The frequency of adverse events was similar in Gatifloxacin- and ciprofloxacin-treated patients, and only slightly higher than in placebo-treated patients. Conclusion. Gatifloxacin was well tolerated in patients with NIDDM controlled by diet and exercise. It had no significant effect on glucose homeostasis, β-cell function, or long-term fasting serum glucose levels, but it did cause a brief increase in serum insulin levels.
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a dose escalation study of the safety tolerability and pharmacokinetics of intravenous Gatifloxacin in healthy adult men
Pharmacotherapy, 2000Co-Authors: Diptee A Gajjar, Frank Lacreta, Georgia Kollia, Howard Uderman, Glenn F Duncan, Martin J Birkhofer, Dennis M GraselaAbstract:Study Objectives. To examine single- and multiple-dose safety, tolerability and pharmacokinetics of Gatifloxacin administered as daily 1-hour intravenous infusions for 14 days, and to determine the effect of Gatifloxacin on glucose tolerance, pancreatic β-cell function, and electrocardiogram (ECG). Design. Randomized, double-blind, placebo-controlled, ascending-dose study. Setting. Bristol-Myers Squibb, Clinical Pharmacology Unit, Princeton, New Jersey, USA. Patients. Forty healthy male subjects, eight in each of five groups, were enrolled to receive sequential doses of Gatifloxacin: 200 mg (10 mg/ml), 200 mg (1 mg/ml), and 400, 600, and 800 mg (2 mg/ml); six subjects per group received active drug and two received placebo. Interventions. A single dose of the drug was administered as an intravenous infusion over 1 hour. After a 72-hour washout period, the drug was administered once/day for 14 days by 1-hour intravenous infusion. Physical examinations, ECGs, spirometry, and clinical laboratory tests, including glucose tolerance test (GTT) and assessment of glucose homeostasis, were performed before treatment and on selected dosing days. A safety evaluation was performed before escalating doses. No intrasubject dose escalation was permitted. Measurements and Main Results. The pharmacokinetics of Gatifloxacin were dose linear and time independent after intravenous administration over the range of 200–800 mg. After daily repeated administration, a predictable, modest accumulation was observed; steady state was reached by the third dose. Approximately 80% of the dose was recovered as unchanged drug in urine. Mean changes (before the first dose to the last dose) after oral GTT and in fasting serum glucose, insulin, and C-peptide concentrations were comparable among the Gatifloxacin and placebo treatment groups. A mild, transient decrease in serum glucose was associated with the end of the 1-hour infusion of Gatifloxacin. No clinically important changes in QTc interval or spirometry occurred. The most frequent treatment-related adverse effects were local intravenous site reactions, which were associated with dose and/or concentration of intravenous solution. Conclusion. Gatifloxacin was safe and well tolerated at intravenous doses of up to 800 mg/day for 14 days. Gatifloxacin pharmacokinetics were linear and time independent.
S. A. Shah - One of the best experts on this subject based on the ideXlab platform.
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tailored Gatifloxacin pluronic f 68 loaded contact lens addressing the issue of transmittance and swelling
International Journal of Pharmaceutics, 2020Co-Authors: Furqan A Maulvi, S. A. Shah, Riya J Parmar, Ankita R Desai, Ditixa M Desai, Manish Shukla, Ketan M Ranch, D O ShahAbstract:Abstract Loading of Gatifloxacin in contact lenses affects critical lens properties (optical and swelling) owing to drug precipitation in the contact lens matrix. The presence of Pluronic® F-68 in the packaging solution creates in-situ micelles in the contact lens to dissolve Gatifloxacin precipitates and provide sustained drug release. The micelles further improved the drug uptake from the drug-packaging solution to create an equilibrium of drug between the lens matrix and the packaging solution. In this study, we optimized Gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and Gatifloxacin loading capacity as well as sustained drug delivery. Optimization of Gatifloxacin-pluronic-loaded contact lens was carried out using a 32 factorial design by tailoring the concentration of Pluronic® F-68 in the packaging solution (X1) and the amount of Gatifloxacin in the monomer solution (X2) to achieve the desired lens properties. The optimized batch (X1 = 0.3%w/v and X2 = 0.3%w/v) showed an optical transmittance of 92.84%, swelling of 92.36% and Gatifloxacin loading capacity of 92.56 μg. The in vitro flux data of the optimized batch (GT-Pl-CL) showed sustained release up to 72 h, whereas soaked contact lenses (SM-CL) and direct Gatifloxacin-loaded contact lenses (DL-CL) showed a sustained release up to 48 h. The in vivo Gatifloxacin release data for rabbit tear fluid showed sustained release with a high Gatifloxacin level for the GT-Pl-CL lens in comparison to the SM-CL and the eye drop solution. This study demonstrates the application of the 32 full factorial design to optimize Gatifloxacin-pluronic-loaded contact lenses to achieve the desired optical transmittance, swelling, and drug loading capacity.
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plackett burman design for screening of critical variables and their effects on the optical transparency and swelling of Gatifloxacin pluronic loaded contact lens
International Journal of Pharmaceutics, 2019Co-Authors: Furqan A Maulvi, S. A. Shah, Riya J Parmar, Ankita R Desai, Manish Shukla, Ketan M Ranch, Ditixa T Desai, Susan Sandeman, D O ShahAbstract:Abstract The optical and swelling properties of Gatifloxacin-loaded contact lens decrease owing to the precipitation of Gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the Gatifloxacin precipitates and not limited to sustain the release of Gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of Gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X 1 , %w/v), the concentration of Pluronic F68 in the packaging solution (X 2, %w/v), the concentration of Gatifloxacin incorporated in the monomer solution (X 3, %w/v), the concentration of Gatifloxacin incorporated in the packaging solution during autoclave (X 4 , %w/v), the concentration of Gatifloxacin incorporated in the packaging solution during extraction (X 5 , %w/v), the time (stabilization time) after the addition of Gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X 6 , h), the pH of the packaging solution (X 7 ), the temperature of the extracted solution (X 8 , °C), and the curing time for fabricating the contact lens (X 9 , min). The Gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y 1 , %), optical transmittances after 7 days of sterilization (Y 2 , %) and swelling percentages after 7 days of sterilization (Y 3 , %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y 1 , Y 2 , and Y 3 , respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X 1 ) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X 2 ) improved them through micelle formation. The other variables (X 3 to X 9 ) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of Gatifloxacin-loaded contact lens.
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determination of Gatifloxacin and ornidazole in tablet dosage forms by high performance thin layer chromatography
Analytical Sciences, 2006Co-Authors: Bhanubhai N. Suhagia, I S Rathod, H M Patel, Dinesh R Shah, S. A. Shah, Bhavin P MaroliaAbstract:A simple and sensitive high-performance thin-layer chromatography (HPTLC) method has been developed for the quantitative estimation of Gatifloxacin and ornidazole in its combined dosage forms. Gatifloxacin and ornidazole were chromatographed on silica Gel 60 F254 TLC plate using n-butanol:methanol:ammonia (6 M) (8:1:1.5 v/v) as the mobile phase and scanned at 302 nm using a Camag TLC Scanner 3. The Rf value of Gatifloxacin and ornidazole was found to be 0.21 ± 0.02 and 0.76 ± 0.04, respectively. The linearity of Gatifloxacin and ornidazole were in the range of 100 - 500 ng/spot and 250 - 1250 ng/spot, respectively. The limit of detection was found to be 40 ng/spot for Gatifloxacin and 100 ng/spot for ornidazole. The proposed method was applied for the determination of Gatifloxacin and ornidazole in combined dosage forms.
David C Hooper - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms and frequency of resistance to Gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2001Co-Authors: Dilek Ince, David C HooperAbstract:Gatifloxacin, an 8-methoxyfluoroquinolone, was found to be two- to fourfold more active against wild-type Staphylococcus aureus ISP794 than its desmethoxy derivative, AM-1121, and ciprofloxacin, another desmethoxy fluoroquinolone. Single grlBA mutations caused two- to fourfold increases in the MIC of Gatifloxacin, and a single gyrase mutation was silent. Double mutations in gyrA and grlA or grlB caused a 32-fold increase in the MIC of Gatifloxacin, in contrast to a 128-fold increase for ciprofloxacin and AM-1121. Overexpression of the NorA efflux pump had minimal effect on the MIC of Gatifloxacin. The bactericidal activity of the three quinolones at four times the MIC differed only for a double mutant, with Gatifloxacin exhibiting a killing pattern similar to that for ISP794, whereas ciprofloxacin and AM-1121 failed to show any killing. With Gatifloxacin, selection of resistant mutants at twice the MIC was 100- to 1,000-fold less frequent than with the comparison quinolones, and mutants could rarely be selected at four times the MIC. The limit resistance in ISP74 was 512 times the MIC of Gatifloxacin and 1,024 times the MICs of ciprofloxacin and AM-1121. Novel mutations in topoisomerase IV were selected in five of the six single-step mutants, three of which were shown to cause quinolone resistance by genetic studies. In conclusion, topoisomerase IV is the primary target of Gatifloxacin. In contrast to comparison quinolones, mutations in both topoisomerase IV and gyrase are required for resistance to Gatifloxacin by clinical breakpoints and do not abolish bactericidal effect, further supporting the benefit of the 8-methoxy substituent in Gatifloxacin.
Daniel P Bonner - One of the best experts on this subject based on the ideXlab platform.
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Bactericidal mechanism of Gatifloxacin compared with other quinolones.
Journal of Antimicrobial Chemotherapy, 2002Co-Authors: Elizabeth Gradelski, B Kolek, Daniel P Bonner, Joan Fung-tomcAbstract:The quinolones differ in their mechanisms of bacterial killing. The rate of bacterial killing by quinolones can be influenced by the addition of bacterial protein or RNA synthesis inhibitors, and the growth phase of the bacterium. In this study, we compared the killing activities of Gatifloxacin, trovafloxacin, ciprofloxacin and norfloxacin against staphylococci, pneumococci and Escherichia coli. Gatifloxacin killing of these organisms occurred regardless of the metabolic state of the microbes. Unlike the comparator quinolones, Gatifloxacin killing was not influenced by the addition of bacterial protein or RNA synthesis inhibitors. Gatifloxacin was able to kill non-dividing staphylococcal and E. coli cells.
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in vitro antibacterial spectrum of a new broad spectrum 8 methoxy fluoroquinolone Gatifloxacin
Journal of Antimicrobial Chemotherapy, 2000Co-Authors: J Fungtomc, B Minassian, B Kolek, Thomas Washo, E Huczko, Daniel P BonnerAbstract:The in vitro antibacterial spectrum of Gatifloxacin was compared with those of ciprofloxacin and ofloxacin. Gatifloxacin was two- to four-fold more potent than comparator quinolones against staphylococci, streptococci, pneumococci and enterococci (Gatifloxacin MIC 90 s, ≤1 mg/L, except 4 mg/L against methicillin-resistant Staphylococcus aureus and Enterococcus faecium). Gatifloxacin was two-fold less potent than ciprofloxacin, and the same as or two-fold more potent than ofloxacin against Enterobacteriaceae (MIC 90 s, 0.06-0.5 mg/L against most members of the Enterobacteriaceae and ≤ 1 mg/L against Proteus/Morganella spp.). Relative to the comparator quinolones, Gatifloxacin was two- to four-fold more potent against Providencia spp., and had good potency against Acinetobacterspp. (MIC 90 s, 0.25-1 mg/L). Gatifloxacin and ofloxacin had similar anti-pseudomonal potency, with corresponding MIC 90 s of 4, 8 and 0.25 mg/L for Pseudomonas aeruginosa, Pseudomonas fluorescens and Pseudomonas stutzeri, while ciprofloxacin had two- to eight-fold more potency. The three quinolones were equipotent against Burkholderia cepacia (MIC 90 s, 8 mg/L), but Gatifloxacin was two-fold more potent against Stenotrophomonas maltophilia (MIC 90 , 4 mg/L). Gatifloxacin was highly potent (MIC 90 s, 0.03-0.06 mg/L) against Haemophilus influenzae, Legionella spp., Helicobacter pylori and had at least eight-fold better anti-chlamydial and anti-mycoplasma potency (Gatifloxacin MIC 90 s, 0.13 mg/L). The higher quinolone MICs for ureaplasma (MIC 90 s, 4-8 mg/L) may be due to the acidic pH of the ureaplasma test medium, which antagonizes quinolones. Like other quinolones, Gatifloxacin had poor potency against Mycobacterium avium-intracellulare, though it was eight- to 16-fold more potent against Mycobacterium tuberculosis (MIC 90 , 0.25 mg/L). Of the three quinolones, only Gatifloxacin had activity against Bacteroides fragilis and Clostridium difficile. In summary, Gatifloxacin is a broad-spectrum 8-methoxy fluoroquinolone that is more potent than ciprofloxacin and ofloxacin against Gram-positive bacteria, chlamydia, mycoplasma, mycobacteria and anaerobes.