I= ICS AND BIOAVAILABILITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGDISPOSITION KINETS,.MEFENAMIC ACID AND PIROXICAM, IN NORMAL, METABOLICALLY ALTERED AND WATER DEPRIVED LABORATORY
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Title of Thesis
ICS AND BIOAVAILABILITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGDISPOSITION KINETS,.MEFENAMIC ACID AND PIROXICAM, IN NORMAL, METABOLICALLY ALTERED AND WATER DEPRIVED LABORATORY

Author(s)
Mrs. Shadab Qamar
Institute/University/Department Details
Faculty of Pharmacy University of the Punjab, Lahore
Session
1996
Subject
Pharmacy
Number of Pages
262
Keywords (Extracted from title, table of contents and abstract of thesis)
NONSTEROIDAL ANTIINFLAMMATORY DRUGS, MEFENAMIC ACID, PIROXICAM, dehydration, febrile, diabetes

Abstract
Two commonly used nonsteroidal anti-inflammatory drugs, mefenamic acid and piroxicam were studied for the alteration in their bioavailability and pharmacokinetic parameters in dehydration, febrile and diabetic states. The effect of these diseases on body weight, blood pH and certain other biochemical parameters were also observed in rabbits. Mefenamic acid and piroxicam in plasma samples were assayed by high performance liquid chromatographic (HPLC) methods.

Paired t-test for the normal and dehydrated state revealed a significant increase in packed cell volume, total proteins, total lipids and blood glucose while a fall in body weight was observed. In case of dehydration, the mean plasma concentration and area under the plasma. Concentration time curve were decreased, but the volume of distribution and total body clearance were increased significantly. These results reflect very well that water deprivation had a profound effect on the pharmacokinetics of the drugs.

A significant decrease in packed cell volume plasma albumin and A/G ratio was measured in febrile rabbits. The animals responded in different ways for the both drugs in fever. The mefenamic acid plasma concentration, area under the plasma concentration time curve and half-life of the drug was increased, whereas the piroxicam plasma concentration levels were decreased. A greater volume of distribution and a longer half-life was observed in endotoxin induced, febrile rabbits, after a single oral dose of piroxicam.

In alloxan treated rabbits the packed cell volume, blood pH and body weight decreased, whereas blood glucose, total lipids, and total proteins increased significantly. The pharmacokinetic behavior of both the drugs was different in diabetes. A significant decrease in plasma mefenamic acid level was observed while plasma concentration of piroxicam increased. The metabolic alteration also influenced the bioavailability and disposition kinetics of both the drugs, which apprise the needs for an adjustment of the dosage regimen under such conditions.

The change in biochemical, bioavailability and disposition kinetic parameters of piroxicam and mefenamic acid during dehydration, fever and diabetes was observed in the present study. However, the clinical implications of the present findings have to await classification and verification in investigations performed in real or clinical dehydration, febrile and diabetic conditions.

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2459.95 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
134.49 KB
2 1 Introduction 1-4
45.82 KB
3 2 Review of literature 5-73
633.81 KB
  2.1 Bioavailability and disposition Kinetics 5
  2.2 Mefenamic Acid 6
  2.3 Piroxicam 26
  2.4 Dehydration condition 50
  2.5 Laboratory model 70
4 3 Materials and methods 74-91
181.71 KB
  3.1 Experimental procedure 74
  3.2 Production of experimental condition 75
  3.3 Study plan 76
  3.4 Sampling procedure 78
  3.5 Analysis of drug 79
  3.6 Biochemical analysis 84
  3.7 Determination of bioavailability and pharmacokinetic parameters 87
  3.8 Statistical analysis 91
5 4 Results and discussion 92-157
775 KB
  4.1 Mefenamic acid 92
  4.2 Piroxicam 125
6 5 Conclusion 158-160
649.36 KB
  5.1 Suggestion 161
  5.2 References 162-202
  5.3 Appendices 203