I= PHARMACOKINETICS OF A NEW QUINOLONE ANTIBIOTIC TOSUFLOXACIN TOSYLATE IN THE PAKISTAN POPULATION
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Title of Thesis
PHARMACOKINETICS OF A NEW QUINOLONE ANTIBIOTIC TOSUFLOXACIN TOSYLATE IN THE PAKISTAN POPULATION

Author(s)
Ali Akbar Sial
Institute/University/Department Details
University of Karachi/ Department of Pharmaceutics
Session
1996
Subject
Number of Pages
219
Keywords (Extracted from title, table of contents and abstract of thesis)
quinolone antibiotic, tosufloxacin tosylate, pyridonecarboxylic acid

Abstract
Tosufloxacin is a new pyridonecarboxylic acid (quinolone) antibiotic with a broad spectrum of antibacterial activity recently developed by Toyama Chemicals Co., Japan, which shows dose dependence and genetic variability in its pharmacokinetics. Several Asian countries are the first ones to market tosufloxacin and thus assessment of its pharmacokinetics is needed in these population. Therefore, a single dose, cross-over comparative study of two brands of tosufloxacin tosylate 150mg tablets was conducted in healthy adult volunteers, as per protocols meeting US FDA guidelines to evaluate pharmacokinetic and bioavailability parameters in Pakistani population

Two tossulfloxacin brands were administered orally separated by one week, being given in a dose of 150 mg. The pharmacokinetics were studied in 14 subjects. Serum samples were collected up to 12 hours and were analyzed as per newly developed microbiological method. Serum concentrations calculated. The absorption rates were much faster i.e., the peak levels of tosufloxacin were 0.72 µg/mL, achieved within four hours. The half-life of about 3.33 hours was in agreement with literature values at all dose levels (300-900 mg). Total body clearance of 25 – 153 liters/hr., distribution volume of 100.04 – 475.00 liters and the AUC was 0.98 – 5.95 µg/mL hr. with 100% relative bioavailability between brands. All of these parameters indicate non-linear kinetics at this dose

Several new methods were used for statistical analysis, including Bayesian theory, the use of confidence intervals and the two one sided test procedures along with ANOVA.The results of the present study indicated no significant difference in the peak concentration (p>0.05) and the area under the cover (p>0.05) of two brands of tosufloxacin 150mg tablets

The partial-area method for bioequivalence assessment was also applied and it was suggested that due to the faster absorption rate and shorter half-life, this method can not be effectively utilized for tosufloxacin bioequivalence study

From these pharmacokinetic and statistical evaluations, we concluded no significant difference between two brands of tosufloxacin studied and thus both the products are said to be bioequivalent in Pakistani population. However, pharmacokinetics at high dose was non-linear

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
193.35 KB
2 1 Introduction 1
817.7 KB
  1.1 Antibacterial Agent 1
  1.2 Quinolones Antibacterial Agents 9
  1.3 Tosufloxacin Tosylate 14
  1.4 Bioequivalence Studies 28
  1.5 Study Objectives 91
3 2 Experimental 93
1726.2 KB
  2.1 Material 93
  2.2 Methods 96
  2.3 Assay Procedure 99