Elevation of high-density lipoprotein in epileptic patients treated with phenytoin

Previous observations have shown that serum alpha (high-density) lipoprotein (HDL) cholesterol is increased by some agents which also act as liver microsomal inducers. Against this background we measured the serum HDL and other lipoprotein and apolipoprotein A levels in 28 epileptic patients who received phenytoin as the only medication. In comparison with healthy controls of similar age and sex, the phenytoin users had significantly higher HDL cholesterol (p less than 0.001) and apolipoprotein A-I (p less than 0.01) levels. Highest values of both parameters were found in patients whose serum phenytoin concentration was within the therapeutic range. HDL cholesterol levels were above the control mean +2 S.D. in 43% of the phenytoin users. Hypertriglyceridemia was more common among male phenytoin users than in control males (33 vs. 16%). It is suggested that phenytoin increases the secretion of nascent HDL particles (and probably also that of VLDL) by the liver and that this could be associated with the induction of hepatic microsomes. Since HDL is inversely reversely related to risk of coronary heart disease, the observed increase of this lipoprotein may be an example of a beneficial side-effect of a drug.