pirozadil (pirozadil / 722D / Calpatil)

Treatment of diet-resistant polygenic hypercholesterolaemic patients with a new nicotinate derivative; in vivo and in vitro low density lipoprotein metabolic studies.

Masana L L, Escobar A A, Joven J J, Solá R R et al.

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 less than 0.02) and Low Density Lipoprotein (LDL) cholesterol from 211.7 +/- 44.9 mg/dl to 168.8 +/- 19.0 mg/dl (P less than 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 significant. 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 less than 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).(ABSTRACT TRUNCATED AT 250 WORDS)

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

Cuchi de la Cuesta C C, Cuchi Alfaro M T MT, Cuchi Alfaro C 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.

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

Effect of pirozadil on lipids, lipoproteins and apolipoproteins in Japanese with type IIa hyperlipoproteinemia.

Shinomiya M M, Ishikawa Y Y, Shirai K K, Saito Y Y et al.

Pirozadil (pyridine 2,6-dimethanol-bis(3,4,5-trimethoxybenzoate), Pemix) was administered for 16 weeks at a dose of 1.5 or 2.0 g/d to 15 adults with Type IIa hyperlipidemia. All patients had achieved a stable weight and were given a diet before treatment. Plasma lipids, lipoproteins and apolipoproteins were measured at 4-week intervals. Pirozadil reduced the mean total cholesterol (TC) level from 291.0 mg/dl to 260.8 mg/dl in 16 weeks (p less than 0.05). The mean percentage decrease was 8.5% in week 16. Low density lipoprotein (LDL)-cholesterol and apolipoprotein B (apoB) decreased 9.7% and 8.5%, respectively, in week 16. A decrease of more than 10% in TC, representing a decrease of more than 30 mg/dl, was observed in 12 of the 15 patients. These 12 patients, who were regarded as responders, showed mean decreases in the levels of TC, LDL-cholesterol and apoB of 13.7%, 10.4% and 11.7%, respectively, but no significant change in the level of high density lipoprotein (HDL)-cholesterol or serum triglycerides. Eight of 11 patients in the lower dose group (1.5 g/d) and all 4 patients who had obtained the higher dose (2.0 g/d) were responders. Suspected side effects of pirozadil were edema, numbness of the extremities and palpitation. The results obtained suggest the beneficial effect of pirozadil on serum lipids in patients with Type IIa hyperlipoproteinemia.