Clofibrate side effects

Disubstituted aryloxyacetic acid derivatives related to clofibrate have been intensively studied in an attempt to get around the side effects of the latter drug. 

A completely different modification of the clofibrate structure was obtained by synthesis of the phenoxy-methylphenoxyisobutyric acids. The 4 -bromo 36 and the 4 -chloro compound 35 were found to be considerably more active than the reference compound clofibrate. But whether definite advantages of these compounds over clofibrate can be demonstrated will be shown only by the current investigations on the mode of action, of side effects and toxicity. 

Peroxisomes enhance the degradation of fatty acids. Consequently, increasing the activity of peroxisomes could help to lower levels of blood triacylglycerides. In fact, clofibrate is rarely used because of serious side effects. 

Clofibrate is tolerated well by must patients the mo.st common side effects are 0.111504 and. to a smaller extent, other gastrointestinal distress. The dosage of anticoagulants, if u.scd in conjunction with this drug, should be reduced by one third to one half, depending on the individual response, so that the prothrombin time may be kept within the desired limits. 

Clofibrate is not used for long-term treatment because of its many side effects such as cardiac dysrhythmias, angina, thromboembolism, and gallstones. 

Etofibrate is an ester incorporating both clofibric acid and nicotinic acid, both of which are released in vivo. One would expect to encounter the side effects of both types of compound the manufacturer s informa-... 

This is chemically 2-acetamido-(p-chloro-phenyl)-(m-trifluoromethylphenoxy)acetate it is thus closely related to clofibrate. Rot-tiers and Van Egmond(15 ) conducted a 48-week double-blind comparison between halofenate and clofibrate, but used only 1 g daily of the former and 2 g daily of the latter. Under these conditions, halofenate had less effect than did clofibrate on triglycerides, and virtually none on cholesterol levels, and one is bound to wonder whether it was not administered in too low a dose. This would explain why halofenate produced no side effects except in one patient who withdrew from the study because of gastric intolerance. The properties of halofenate are probably very similar to those of clofibrate, and its ability to potentiate the effects of anticoagulants and sulphonylureas (see above) has apparently been demonstrated (12 =). 

This is the dimethylbutyramide ester of C.P.I.B., i.e. it releases the same active metabolite as clofibrate, and apparently at about the same rate. The recommended dose is somewhat lower than that of clofibrate, and this (as well as the more limited experience with the drug) is probably the main reason why there is as yet little information on side effects. In theory, the release of dimethylbutyramide as the drug dissociates might lead to unexpected side effects. Foucault (16 ), who treated 32 patients for 3 months or longer with clofibride, but who does not indicate the exact dose employed, recorded gastric symptoms in 4 cases, diarrhoea in one and somnolence in one another more important was the fact that a third of the patients admitted to experiencing cramps in the... 

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