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Title of Thesis

A Study of Pioglitazone Biokinetics, Renal Clearance and its Effect on Glycation Level

Author(s)

 Muhammad Alim

Institute/University/Department Details

Department of Chemistry and Biochemistry / University of Agriculture Faisalabad

Session
2009

Subject

Chemistry

Number of Pages
318
Keywords (Extracted from title, table of contents and abstract of thesis)
Pioglitazone, Biokinetics, Renal, Clearance, Effect , Glycation, Level

Abstract

Pioglitazone is an oral anti-diabetic agent which belongs to a class “thiazolidinediones”. It is used in the treatment of type 2 diabetes mellitus. It acts primarily by increasing peripheral sensitivity to insulin through binding to peroxisome proliferators activated receptor gamma. In recent years, due to variation in pharmacokinetic parameters under different environmental conditions, drug pharmacokinetics has received increasing attention. Therefore, the present study was designed to evaluate the biokinetics, renal clearance and effect on glycation level of pioglitazone in human beings under indigenous conditions. After through clinical examination healthy male volunteers (n = 24), female volunteers (n = 12) and diabetic patients (n = 8) were selected for the study. Each volunteer was given a therapeutic dose of 30 mg pioglitazone tablet orally. Patients were given a dose of 30 mg pioglitazone daily up to 12 weeks. In healthy volunteers scheduled plasma and urine samples were collected at different time intervals. Concentration of pioglitazone in plasma and urine samples was determined by validated high performance liquid chromatographic method. For the estimation of renal clearance of pioglitazone, the endogenous creatinine level was measured in plasma and urine samples spectrophotometrically using kit method based on Jaffe reaction. In plasma samples obtained from healthy volunteers and patients, amount of glucose was estimated by kit method, proteins by Biuret method and glycation level was measured by Thiobarbituric acid (TBA) method, spectrophotometerically. Both differences and similarities are present in the values of different calculated parameters and the values reported in the literature. After comparison minor sex differences were also found to be present in the values of different calculated parameters but statistically these differences were found to be non-significant. A single dose of pioglitazone (30 mg) has no effect on glucose concentration and glycation level in healthy male volunteers. Long term treatment of pioglitazone in diabetic patients, significantly decreased the glucose concentration and glycation level. This indicates that pioglitazone acts as an inhibitor of glycation.

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1772 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 CONTENTS 13
130 KB
2 1 INTRODUCTION 7
97 KB
3 2

REVIEW OF LITERATURE

2.1 Chemistry of drug

2.2 Diabetes mellitus

2.3 Prevalence of diabetes mellitus

2.4 Pioglitazone and type 2 diabetes mellitus

2.5 Mechanism of action of pioglitazone

2.6 Adverse effects of pioglitazone

2.7 Methods for the measurement of pioglitazone

2.8 Pharmacokinetics/ biokinetics of pioglitazone

2.9 Pharmacokinetic parameters of pioglitazone

2.10 Renal clearance

2.11 Renal clearance of endogenous creatinine

2.12 Glycation

2.13 Glycation of plasma proteins

2.14 Chemistry of Maillard reaction

2.15 Inhibitors of glycation

2.16 Pioglitazone as an inhibitor of glycation

2.17 Determination of glycation level

2.18 Measurement of glucose

2.19 Determination of proteins concentration

 

49
438 KB
4 3

MATERIALS AND METHODS

3.1 Biokinetics/pharmacokinetics of pioglitazone

3.2 Renal clearance of pioglitazone and creatinine

3.3 Urinary excretion of pioglitazone

3.4 Effect of pioglitazone on glycation level

3.5 Statistical methods

 

27
203 KB
5 4

RESULTS AND DISCUSSION

4.1 Validation of analytical method

4.2 Biokinetics/pharmacokinetics of pioglitazone

4.3 Renal clearance of pioglitazone

4.4 Urinary excretion of pioglitazone

4.5 Effect of pioglitazone on glycation level

57
439 KB
6 5 SUMMARY 3
  5.1 LITERATURE CITED 152
693 KB