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Title of Thesis

Arshad Ali
Institute/University/Department Details
University of Karachi/ Department of Chemistry
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
cephalosporin, cefixime, cephalexin, cefazoline, cefotaxime, ceftazidime, cimetidine, ranitidine, famotidine, ceftazidime, h2-receptor

The research work comprises of interaction studies of five comphalosporins i.e., cefixime, cephalexin, cefazoline, cefotaxime and ceftazidime with H2-receptor antagonists and essential & trace elements

Cephalexin and cefazolin belong to first generation, while cefixime, cefotaxime and ceftazidime are classified in third generation of antibiotics. All these cephalosporins are derived from 7-aminocephalosporanic acid (7-ACA) while the penicillins are derived from 6-aminopenicillanic acid (6-APA).Both structures contain the basic B-lactam ring but the cephalosporin structure allows for more Gram-negative activity than the penicillins and aminocillins. Substitution at “R” sites (different side chains) allows for variation in the spectrum of activity and duration of action

H2-receptor antagonists are commonly prescribed to patients complaining of Gi irritations, which may be a consequence of leasions or inflammations in the tract. In addition, all cephalosporins cause gastric upset even in normal subjects. H2-receptor antagonists may be coadministered in patients having cephalosporin therapy and complaining about gastric irritations specially the peptic ulcer patients, who are the real victims of this simultaneous drug therapy. The behavior of three most commonly used H2-receptor antagonists, cimetidine, ranitidine and famotidine in presence of these cephalosporins was studied by using standard dissolution apparatus in simulated gastric juice and in buffer of pH 7.4 simulating blood pH, at three different temperatures (37, 60 & 100C) simulating body temperature as well as accelerated temperatures studies. Furthermore, the stability of each drug in presence of interacting drugs had also been studies. These interaction studies with H2-receptor antagonists in gastric as well as blood pH revealed that simultaneous use of these drugs depressed the availability of the antibiotic as well as cimetidine, ranitidine and famotidine

Since the presence of complexing ligand may affect the bioavailability of a metal in the blood or tissues, therefore, in order to study the probable interaction of cephalosporins with essential and trace elements present in human body, synthesis of drug metal complexes of these cephalosporins were also carried out with essential and trace elements. The elements used were magnesium, calcium, chromium, manganese, iron, cobalt nickel, copper, zinc and cadmium in the from of their hydrated salts. These synthesized complexes were analyzed for their purity, melting points and solubility in various polar and non-polar solvents. The structures of these complexes were established by CHN analysis and by estimating the metal incorporated in the drug-metal complex by atomic absorption spectroscopy. The infrared spectrophotometric studies of these complexes as compared to parent drugs supported to ascertain the site of coordinating ligand. It has been observed that the complexes of these cephalosporins the drug molecule serves as a bidentate ligand coordinating through both its carboxyl group of six membered dehydrothiazine ring and B-lactam nitrogen with the metal having a square planar or octahedral geometry

Our investigations reveal that formation of complexes results in decrease in antibacterial activity of these cephalosporins as MIC values are increased. Hence there are reasons to believe that these minerals and trace elements interact with the antibiotic and affect the antibiotic levels. Moreover, this simultaneous therapy not only affects the antibiotic levels, but also depletes the supplemented essential trace elements. This phenomenon may happen even in the absence of any multiple drug administration and can drain the essential trace elements of the body.

These results clearly indicate a warning against multiple drug therapy, while extreme care is needed in case of prescribing them with ceftazidime as well as other third generation antibiotics

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4056.56 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
210.13 KB
2 1 Introduction 1
601.69 KB
  1.1- A Cephalosporins 6
  1.2-B Cefixime 18
  1.3-C Cephalexin 27
  1.4-D Cefazolin 38
  1.5-E Cefotaxime 46
  1.6-F Ceftazidime 58
3 2 H2-Receptor Antagonists 67
42.84 KB
  2.1 Cimetidine 68
  2.2 Ranitidine 69
  2.3 Famotidine 70
4 3 Trace And Essential Elements 71
153.86 KB
5 4 Drug Interactions 86
13.96 KB
6 5 Objectives Of Present Work 87
19.21 KB
7 6 Experimental 89
230.3 KB
  6.1- A Materials 89
  6.2-B Methods 91
  6.3-C Synthesis Of Cephalosporin Metal Complexes 95
  6.4-D Analysis Of Cephalosporin Metal Complexes By Aa Spectrometry 107
  6.5-E Antibacterial Studies 108
8 7 Results And Discussion 113
2423.9 KB
  7.1-A Cefixime H2-Receptor Antagonist Interactions 180
  7.2-B Cephalexin H2-Receptor Antagonist Interactions 210
  7.3-C Cefazolin H2-Receptor Antagonist Interactions 212
  7.4-D Cefotaxime H2-Receptor Antagonist Interactions 214
  7.5-E Ceftazidime H2-Receptor Antagonist Interactions 216
  7.6-F H2-Receptor Antagonists In Presence Of Cephalosporins 219
9 8 References 415
930.5 KB