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

Mrs. Shadab, Qamar (1996) ICS AND BIOAVAILABILITY OF NONSTEROIDAL ANTIINFLAMMATORY DRUGDISPOSITION KINETS,.MEFENAMIC ACID AND PIROXICAM, IN NORMAL, METABOLICALLY ALTERED AND WATER DEPRIVED LABORATORY. Doctoral thesis, University of the Punjab, Lahore.

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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.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: NONSTEROIDAL ANTIINFLAMMATORY DRUGS, MEFENAMIC ACID, PIROXICAM, dehydration, febrile, diabetes
Subjects: R Medicine > RM Therapeutics. Pharmacology
Depositing User: Muhammad Khan Khan
Date Deposited: 25 Oct 2016 08:10
Last Modified: 25 Oct 2016 08:10
URI: http://eprints.hec.gov.pk/id/eprint/2686

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