Drug treatment of lipoproteinaemia type II. Effect on plasma lipids of a new phenoxyacetic acid derivative, clofibrate, and nicotinic acid

Abstract

The plasma lipid-reducing effect of a new phenoxyacetic acid derivative (GP 45.699) has been studied in nine patients with lipoproteinaemia Type II A or Type II B. GP 45, 699, 0.75 g per day produced a marked (average 26%) fall in the plasma cholesterol. Doubling the dose led to further reduction of cholesterol, but plasma triglycerides rose. This was associated with an increase in plasma triglyceride turnover as measured by an intravenous fat-loading test (Intralipid), an elevation in serum simplastin A, and with a rise in the SGOT and SGPT levels. — It is suggested that GP 45.699 which is related chemically to clofibrate, has a marked effect on cholesterol catabolism and on the rate of turnover of plasma triglycerides. It also affects liver cells causing increased synthesis of plasma triglycerides or pre-beta-lipoprotein, and, in some cases receiving high doses (1.5 g daily), there may also be liver damage. Despite its promising capacity to reduce the plasmacholesterol level, there may not be sufficient justification for its routine use in cases of lipoproteinaemias.