Thesis
Analysis and Pharmacokinetics of non-steroidal anti-inflammatory drug combinations in man
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 1988
- Thesis identifier
- T6636
- Qualification Level
- Qualification Name
- 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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