Sex-related differences in the impairment of hepatic drug-metabolizing enzymes in rats with adjuvant disease

The pharmacokinetics and metabolism of tolmetin, a non-steroidal anti-inflammatory drug, were studied in healthy control and adjuvant arthritic (AA) female Lewis rats. Tolmetin was rapidly and completely absorbed by both groups of rats. Peak plasma concentrations of tolmetin and the area under the tolmetin plasma concentration -time curve (AVC) were significantly (p < .05) decreased in AA rats after a single oral dose of tolmetin sodium (50 mg/kg). Fourteen days of treatment at 50 mg/kg/day caused no significant change in these parameters. The plasma protein binding of tolmetin was decreased three to five fold in AA rats as compared with healthy controls. This was reflected in an increase in volume of distribution (Vd) for tolmetin and a marked increase in renal clearance (CIR) of tolmetin for AA rats. Plasma hepatic clearance (Clp,Hlf) was increased for AA rats, indicating no decrease in hepatic functon for AA rats. The dicarboxylic acid metabolite (MCPA) also had decreased peak concentrations and AVC in AA rats with an increase in oral plasma clearance (CI PIc) and CI R. However, excretion of MCPA conjugates in feces was reduced ten fold with a concomitant increase in urinary tolmetin due to the marked increase in tolmetin CI R for AA rats.

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“…This is in contrast to the findings of other studies (9)(10)(11) in which decreased metabolism of drugs was noted in AA rats.…”

Section: Discussioncontrasting

confidence: 99%

Pharmacokinetics and metabolism of tolmetin in normal and adjuvant arthritic Lewis rats

Grindel

Migdalof

Yorgey

et al. 1982

European Journal of Drug Metabolism and Pharmacokinetics

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“…Many studies [5,[23][24][25] have shown that during the development of arthritic disease in the rat, there is a wide range of biochemical and clinical alterations. The bacterial antigen, recognised as a foreign substance by the hosts, immunological system, induces a sequence of stereo-typed cyclic changes of clinical manifestations.…”

Section: Discussionmentioning

confidence: 99%

Studies on carbohydrate moieties of glycoproteins in established adjuvant induced arthritis

Reddy

Dhar

1988

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The investigation presents the metabolic changes in the carbohydrate components of glycoproteins in several tissues of adjuvant arthritic rats. The experimental arthritis induces a significant modification of total carbohydrate moieties of glycoproteins in arthritic tissues. In both acute and chronic phases of the disease, the adjuvant arthritis caused a significant increase in the levels of carbohydrate moieties of tissue glycoproteins viz. total hexose, hexosamine, fucose, sialic acid, total neutral sugar content and neutral sugar monosaccharides. In addition, the urinary excretions of hexosamine and uronic acid in arthritic rats were found to be elevated significantly. The data from the investigation clearly indicate that the experimental arthritis induces an increased glycoprotein synthesis in most of the tissues examined.

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Effect of honeybee (apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat

Eiseman

Bredow

Alvares

1982

Biochemical Pharmacology

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Sex-related differences in the impairment of hepatic drug-metabolizing enzymes in rats with adjuvant disease

Cited by 4 publications

References 6 publications

Pharmacokinetics and metabolism of tolmetin in normal and adjuvant arthritic Lewis rats

Pharmacokinetics and metabolism of tolmetin in normal and adjuvant arthritic Lewis rats

Studies on carbohydrate moieties of glycoproteins in established adjuvant induced arthritis

Effect of honeybee (apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat

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