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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 535-539 
    ISSN: 1432-1041
    Keywords: Apolipoproteins ; Hypercholesterolaemia ; Pravastatin ; lipids ; lipoproteins ; probucol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of co-administration of low doses of pravastatin to hypercholesterolaemic patients already receiving long-term probucol treatment (mean 500–1,000 mg/day for 350 days) were investigated. Pravastatin 5 mg/day (Group 1; 12m, 13f; mean age 59.1 y) or 10 mg/day (Group 2; 8m, 11f; mean age 60.8 y) was administered, and blood was taken after 0, 3, 6, and 12 months. Both groups showed a significant reduction in serum total cholesterol (TC), phospholipid (PL), low density lipoprotein-cholesterol (LDL-C), LDL-triglyceride (TG), LDL-PL, apolipoprotein (apo) B, and apo E after the combined therapy. These levels were reduced more in Group 2 than in Group 1 subjects. In Group 2, significant falls in serum TG and apo CII were also observed. The changes in TC, PL, LDL-C, apo B, apo CII and apo E were dependent upon the dose of pravastatin, as assessed by two-way analysis of variance. Serum high density lipoprotein (HDL)3-C, apo AI and apo AII were slightly but significantly increased in both groups after 12 months of combined therapy, but the increase was not sufficient to reverse the probucol-induced lowering of the HDL level. We conclude that combined therapy resulted in a significant reduction in atherogenic lipoproteins and apolipoproteins, and an increasing dose of pravastatin (5 mg to 10 mg daily) made the lipid lowering effect more prominent. The reduction in serum HDL-C due to long-term probucol administration was not reversed by the addition of pravastatin.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1041
    Keywords: Bezafibrate ; Hypercholesterolaemia ; Probucol ; apolipoproteins ; lipids ; lipoproteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effects of the administration of slow-release bezafibrate to hypercholesterolaemic patients who were already receiving long-term probucol treatment (mean 865 days, 500–1000 mg·day−1) were investigated. Bezafibrate was administered at either 200 mg·day−1 (13 males, 13 females, mean age 55.2 years) or 400 mg·day−1 (11 males, 14 females, mean age 57.2 years), and blood was taken at 0, 3, 6 and 12 months after the beginning of combination therapy. Overall, serum total cholesterol (TC), triglyceride (TG), very low density lipoprotein (VLDL)-TC, high-density lipoprotein (HDL)-TG, VLDL-TG, VLDL-phospholipid (PL), lipoprotein (a) [Lp(a)], apolipoprotein (apo) C-III, apo E levels and LCAT activity decreased significantly with this combination therapy, while HDL cholesterol (C), HDL3-C, HDL-PL, apo A-I and apo A-II levels significantly increased, as assessed by analysis of variance (ANOVA). Five patients (one receiving 200 mg·day−1, four receiving 400 mg·day−1 bezafibrate) showed drastic reductions in HDL-C (HDL-C levels were reduced by a mean of 46.2%, 59.3% and 61.6% at 3, 6 and 12 months, respectively) after beginning combination therapy. These HDL-C reductions were maintained for the 1 year of combination therapy, but then returned to pre-combination treatment levels 1 month after discontinuation of bezafibrate. Serum probucol concentrations and cholesteryl ester transfer protein (CETP) mass were assayed at 6 months, and the probucol concentration was higher in the HDL-deficient group (56.2 vs 26.5 μg/ml). In contrast, CETP mass was significantly lower in HDL-deficient patients than in non-HDL-deficient patients (2.08 vs 2.87 mg·l−1). When the patients in the non-HDL-deficient group were divided into two groups, receiving low (200 mg·day−1, n−25) and high (400 mg·day−1, n−21) doses of bezafibrate, the former group showed a significant increase in probucol-lowered HDL-C and apo A-I, although these levels did not return to pre-probucol treatment levels, while the latter group showed no changes in HDL. These data suggest that the addition of a low dose of bezafibrate to probucol tended to reverse probucol-induced HDL lowering, while 9.8% (5 of 51 patients) of the patients exhibited a severe HDL deficiency. Since it is unclear whether or not such an extreme HDL reduction is harmful, HDL deficiency should be carefully monitored with this combination therapy.
    Type of Medium: Electronic Resource
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