In the present study, the effect of probucol (500mg×2, daily) on serum lipids and lipoproteirs level were studied in 9 patients with familial hypercholesterolemia (FH) during 3-4 months. The diagnosis of FH was established according to the criteria both of Fredrickson et al and of Makuchi et al. Thickness of Achilles tendon was over 9mm in all patients and the xanthomas were observed in 4 of 9 patients.
Before and 3-4 months after treatment of probucol the measurement of serum triglyceride (TG), total cholesterol (TC) and apolipoprotein (Apo) A-I and A-II were made. At the same time, serum VLDL, LDL, HDL2 and HDL3 were separated by successive ultracentrifugation. Thereafter, TG, TC and protein of each lipoprotein fraction were measured.
TG and TC were determined by enzymatic method, Apo A-I and A-II were done by single immunodiffusion assay, and protein was done by dye-binding method.
All data were expressed as mean ±S.E. and statistically analized by Student's t-test.
The results were as follows:
1) VLDL-TG levels were slightly increased, although no significance was found between VLDL-TG level before and after treatment.
2) The levels of serum TC were 388±37mg/dl and 308±28mg/dl (-21%, p<0.05) before and after probucol administration, respectively. LDL-cholesterol (LDL-C) levels decreased from 325±37mg/dl before treatment to 262±32mg/dl (-19%, p<0.05) after treatment. HDL-C values significantly decreased from 42±5mg/dl to 26±4mg/dl (-38%, p<0.01), and especially HDL2-C showed significant fall (-48%, p<0.01).
3) Serum Lecithin: Cholesterol Acyltransferase (LCAT) activities were not changed.
4) The concentrations of Apo LDL decreased from 139±18mg/dl to 106±17mg/dl (-29%), but it was not significant statistically. Apo A-I levels decreased significantly from 92±10mg/dl to 66±10mg/dl (-28%, p<0.01). On the other hand, Apo A-II levels were unchanged.
These observations suggested that probucol would be a useful drug to improve serum and LDL cholesterol levels in FH. However, we should take care to use this drug because of its effect on HDL metabolism.
