Thesis

Analysis and Pharmacokinetics of non-steroidal anti-inflammatory drug combinations in man

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Awarding institution
  • University of Strathclyde
Date of award
  • 1988
Thesis identifier
  • T6636
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Department, School or Faculty
Abstract
  • High Performance Liquid Chromatographic methods for quantifying 11 commonly used non-steroidal antiinflammatory drugs in serum were developed. Rapid, specific and sensitive adaptations of the methods were achieved by extraction with chloroform : acetonitrile 3:2 or diethylether : n-hexane 1:1 , giving recoveries of 85-98 %. The methods were used to study the in-vivo kinetic properties of aspirin in healthy volunteers when aspirin (652mg) was taken alone (I), with paracetamol (l000mg) (II) or with indomethacin (l00mg) (III) The salicylate absorption rate for I was 0.75 ± 0.03 hr⁻¹ (mean ± S.E.M) but for II the absorption rate was 0.99 ± 0.03 hr⁻¹ ; for III the absorption rate was 1.14 ± 0.05 hr⁻¹ These constants for II and III were different (p = 0.05) from that for I but not from each other. Statistically significant differences were not found between other pharmacokinetic parameters viz: (mean ± S. E. M. ) I II II Distribution Volume ( L ) 8.60 ± 0.79 : 7.97 ± 0.57 : 7.27 ± 0.45 : Rate (hr⁻¹) blood to tissue 0.07 ± 0.02 : 0.11 ± 0.02 : 0.23 ± 0.03 : Tissue to blood 0.15 ± 0.01 : 0.20 ± 0.02 : 0.23 ± 0.03 : Elimination rate (hr⁻¹) Pseudodistribution ( body) 0.08 ± 0.01 : 0.08 ± 0.01 : 0.09 ± 0.01 : Central compartment (plasma) 0.12 ± 0.01 : 0.13 ± 0.02 : 0.13 ± 0.01 Relating the findings to changes in electropotential differences across the gastric mucosa it is apparent that a reduced gastric mucosal distribution of aspirin with an increased intestinal mucosal transport of aspirin when combined with paracetamol or indomethacin confer protective effect on the gastric mucosa.
Resource Type
DOI
EThOS ID
  • uk.bl.ethos.291891
Date Created
  • 1988
Former identifier
  • 65599

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