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

Muhammad, Alim (2009) A Study of Pioglitazone Biokinetics, Renal Clearance and its Effect on Glycation Level. PhD thesis, University of Agriculture, Faisalabad .

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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.

Item Type:Thesis (PhD)
Uncontrolled Keywords:Pioglitazone, Biokinetics, Renal, Clearance, Effect , Glycation, Level
Subjects:Physical Sciences (f) > Chemistry(f2)
ID Code:2840
Deposited By:Mr. Javed Memon
Deposited On:20 Feb 2010 13:42
Last Modified:20 Feb 2010 13:42

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