Isomer effects on metabolism

Isomer effects on metabolism Isomer effects on uptake Isomer effects on excretion Practical considerations A Racemates or enantiomers ... 

Goldstein, J.A., J.D. McKinney, G.W. Lucier, P. Hickman, H. Bergman, and J.A. Moore. 1976. Toxicological assessment of hexachlorobiphenyl isomers and 2,3,7,8-tetrachlorodibenzofuran in chicks. II. Effects on drug metabolism and porphyrin accumulation. Toxicol. Appl. Pharmacol. 36 81-92. 

As well as an effect on the activity, different stereoisomers will also exhibit differences in other physiochemical properties, such as absorption, metabolism and elimination. For example, (—)norgestrel is absorbed at twice the rate of (+)norgestrel through buccal and vaginal membranes. The plasma half life of S-indacrinone is 2-5 hours whilst the value for the R isomer is 10-12 hours. 

The research on CLA in growing animals is consistently showing effect on modulation of body mass and fat, however, the effect in humans is not consistent. More research is needed to delineate the effect of CLA and isomers on body composition in humans. Major research emphasis, at present, is focused on the effects of CLA and its isomers on body composition and carcinogenesis. Other areas that are attracting attention include the effects of CLA and isomers on cardiovascular, metabolic, and immune functions and the strategies to increase the content of CLA isomers in meat and dairy products. 

In an intestinal perfusion study of the effect of ketoconazole 40 pg/ml on the jejunal permeability and first-pass metabolism of (R)- and (5)-verapamil 120 pg/ml in six healthy volunteers, ketoconazole did not alter the jejunal permeability of the isomers, suggesting that it had no effect on the P-glycoprotein mediated efflux. However, the rate of absorption increased, suggesting inhibition by ketoconazole of the gut wall metabolism of (i /5)-verapamil by CYP3A4 (35). 

Other Test Items and Precautions. These examine the effects on drug metabolic enzymes, drug interaction and the first pass effect as required. In case of race-mates, the differences of pharmacokinetics between isomers should be examined by quantifying each isomer separately. 

Sigmoid Emax Model Jonkers and colleagues [80] studied the pharmacodynamics of racemic metoprolol, a cardioselective beta-blocker, and the active S-isomer in extensive metabolizers (EMs) and poor metabolizers (PMs). The drug effect studied was the antagonism by metoprolol of terbutaline-induced hypokalemia (abnormally low potassium concentration in the blood). The pharmacodynamic interaction was described by a sigmoidal function for competitive antagonism based on the earlier work of Holford and Sheiner [81] ... 

Because the metabolism of trans-18 1 to stearic acid is thought to be the rate-limiting step in complete BH (Keeney, 1970), the effects of diet on lipid metabolism in the rumen tend to have a more pronounced effect on the amount and relative proportions of trans-18 1 leaving the rumen than on other BH intermediates including isomers of CLA. With respect to enhancing RA content of ruminant foods, it could be argued that the most important aspects of dietary effects on ruminal BH relate to those on VA and the factors that regulate its synthesis. 

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