Treatment of Diet‐Resistant Polygenic Hypercholesterolaemic Patients with a New Nicotinate Derivative; In Vivo and In Vitro Low Density Lipoprotein Metabolic Studies

Q3 · MEDICINE

Article

Author: E. Vilella ; P. R. Turner ; A. Escobar ; J. Joven ; T. Bargallo ; L. Masana ; R. Sola

Six patients (four women and two men) with mild to moderate hypercholesterolemia, but with no clinical evidence of the disease being monogenic familial hypercholesterolaemia and who, over the previous 3 months on a rigidly controlled hypolipidaemic diet therapy, showed no reduction in plasma cholesterol levels, were recruited into a study to assess the metabolic effects of Pirozadil, a new nicotinic acid derivative. After a 3 month treatment period, a significant reduction in plasma cholesterol from 299.8 ± 31.2 mg/dl (mean ± SD) to 256.8 ± 18.1 mg/dl (P < 0.02) and Low Density Lipoprotein (LDL) cholesterol from 211.7 ± 44.9 mg/dl to 168.8 ± 19.0 mg/dl (P < 0.05) was observed. Although there was a trend toward decreased plasma and Very Low Density Lipoprotein (VLDL) triglyceride, the differences did not reach statistical significance. High Density Lipoprotein (HDL) cholesterol was unchanged. The drug was well tolerated with no side effects noted. To assess the mode of action, autologous125I‐labelled LDL was injected and apoprotein B (apo B) kinetic parameters were measured; production rate (PR) and fractional catabolic rate (FCR). An in vitro measurement of the in vivo catabolism (LDL‐apo B receptor activity in freshly isolated lymphocytes) was also measured pre‐ and post‐treatment. The pharmacological intervention resulted in a significant decrease of 19.9% in PR from 10.5 ± 1.81 mg/kg/d to 8.41 ± 1.13 mg/kg/d (P < 0.05) while the FCR remained relatively unchanged (0.260 ± 0.042 vs 0.248 ± 0.040 pools/d) as did the LDL receptor activity (78.2 ± 20.9 vs 69.3 ± 21.4 ng LDL/mg cell protein/hr). Our data suggest that in polygenic hypercholesterolaemia, a condition in which the LDL receptor and hence catabolism is normal, the alternative therapy to facilitating enhanced catabolism is one that decreases the synthesis of the lipoprotein and, as such, nicotinic acid and its derivatives may be effective hypolipidaemic agents.

01 Jan 1989·Revista clinica espanolaQ4 · MEDICINE

[Clinical evaluation of pirozadil, administered continuously over four and a half years, in patients with hyperlipoproteinemia type IIa].

Q4 · MEDICINE

Article

Author: Cuchi Alfaro, M T ; Cuchi de la Cuesta, C ; Cuchi Alfaro, C

With the goal to evaluate the long term efficacy and tolerance of pirozadil, 20 patients with hypercholesterolemia (type II a hyperlipoproteinemia) received this drug for 4.5 years. Lipidic parameters and the appearance of subjective manifestations related to the drug were periodically controlled. The triglyceride concentration (34%), total cholesterol (24%) and LDL-cholesterol (47%) decreased after 6 months of treatment with 1.5 to 2 g/day of pirozadil. These changes were more manifest during the second semester of therapy and did not show important oscolations in subsequent controls. Adverse effects, indicating the withdrawal of the drug were not encountered. Three patients had minor and transient epigastralgias. Taken as a whole, these results reinforce the usefulness of pirozadil in treating patients with hypercholesterolemias.

12 Dec 1987·Medicina clinicaQ4 · MEDICINE

[Efficacy and tolerance to pirozadil over a long term. Drug surveillance study. The Pirozadil Drug Surveillance Group].

Q4 · MEDICINE

Article

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