Characterization of apoprotein metabolism and atherogenic lipoproteins during oral isotretinoin treatment.

Apoprotein, lipoprotein and lipid parameters of 36 normolipidemic subjects (23 males, mean age 22.7 +/- 7.6 years; 13 females, mean age 26.2 +/- 9.8 years) receiving oral isotretinoin (mean daily dose 0.73 +/- 0.26 mg/kg body weight) for nodulocystic acne (n = 18), severe acne papulopustulosa (n = 15), gram-negative folliculitis (n = 2) and papulopustular rosacea (n = 1) were monitored before and during isotretinoin therapy at biweekly intervals over a period of 14.6 +/- 5.6 weeks. Pretreatment values of mean plasma triglycerides increased significantly (p less than 0.001) from 81.8 +/- 31.9 mg/dl to 112.4 +/- 38.7 mg/dl (47.4%) during isotretinoin treatment. With respect to the mean percent increase of plasma triglycerides from pretreatment levels, patients were classified as nonresponders (less than 10% triglyceride increase), responders (greater than 10% less than 50% triglyceride increase) and hyperresponders (greater than 50% triglyceride increase), revealing a distribution of 25.0, 36.1 and 38.9%, respectively. Isotretinoin treatment had no influence on the isoelectric focusing pattern of apoprotein E isoforms and C apoproteins. In particular, apoprotein C-II, the cofactor of lipoprotein lipase, was not affected. No correlation between apoprotein E phenotypes (2/3, 3/3, 3/4) and the mean plasma triglyceride increase could be demonstrated. Apoprotein B-48, a marker of chylomicrons and atherogenic chylomicron remnants, could not be detected by SDS-PAGE. On the other hand in 21.0% of patients with preexisting mean lipoprotein Lp(a) levels of 18.1 +/- 12.9 mg/dl a moderate increase of atherogenic Lp(a) to mean levels of 37.0 +/- 22.0 mg/dl was observed. Pretreatment values of very-low-density lipoprotein (VLDL) apoprotein (apo) B (7.5 +/- 2.0 mg/dl), low-density lipoprotein apo B (67.3 +/- 17.5 mg/dl) and total plasma apo B (76.6 +/- 19.0 mg/dl) increased significantly to levels of 10.3 +/- 2.4 mg/dl (p less than 0.001), 75.7 +/- 15.8 mg/dl (p less than 0.10) and 85.9 +/- 17.7 mg/dl (p less than 0.05), respectively. As lipoprotein lipase and hepatic lipase activities have been shown to be unaffected by isotretinoin treatment, our data support the hypothesis that isotretinoin induces hepatic oversecretion of VLDL, a condition resembling type IV hyperlipidemia in diabetics, familial hypertriglyceridemia of familial combined hyperlipidemia.