Homocysteine elevation with fibrates: is it a class effect?
BACKGROUND
Case-control and prospective studies indicate that an elevated plasma homocysteine level is a powerful risk factor for atherosclerotic vascular diseases. Certain medications can induce hyperhomocystinemia, such as methotrexate, trimethoprim and anti-epileptic drugs. There are few reports indicating an interaction between lipid-lowering drugs (cholestyramine and niacin) and homocysteine. Recently, an interaction was shown between fenofibrate and benzafibrates (a fibric acid derivative) and homocysteine plasma levels.


OBJECTIVE
To evaluate the effects of different fibrates on plasma homocysteine levels and to measure the reversibility of this effect.


RESULTS
We investigated the effects of ciprofibrate and bezafibrate on homocysteine levels in patients with type IV hyperlipidemia and/or low high density lipoprotein levels. While a 57% increase in homocysteine was detected in the ciprofibrate-treated group (n = 26), a 17% reduction in homocysteine was detected in the group treated with bezafibrate (n = 12). The increase in homocysteine in the ciprofibrate-treated group was sustained for the 12 weeks of treatment and was partially reversible after 6 weeks of discontinuing the ciprofibrate therapy.


CONCLUSIONS
These results indicate that an increase in plasma homocysteine levels following administration of fibrates is not a class effect, at least in its magnitude. Moreover, it is reversible upon discontinuation of the treatment.
Harats
D
D
Institute of Lipid and Atherosclerosis Research, Sheba Medical Center, Tel-Hashomer, Israel. dharats@post.tau.ac.il
Yodfat
O
O
Doolman
R
R
Gavendo
S
S
Marko
D
D
Shaish
A
A
Sela
B A
BA
D000328:Adult; D001629:Bezafibrate / Q000627:therapeutic use*; D002995:Clofibric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D058607:Fibric Acids; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D004041:Dietary Fats; D058607:Fibric Acids; D000960:Hypolipidemic Agents; D014280:Triglycerides; D006710:Homocysteine; D002995:Clofibric Acid; C019304:ciprofibrate; D001629:Bezafibrate