Bioavailability and Pharmacokinetics in Man of Acipimox, a New Antilipolytic and Hypolipemic Agent

Abstract

Two separate studies were performed: in the first study for healthy male volunteers received three single oral doses (150, 250 and 400 mg) of 5-methylpyrazine carboxylic acid 4-oxide (acipimox) according to a randomized sequence. Plasma levels of the drug were determined by RIA and urinary excretion by HPLC. In the second trial the effect of food on the drug bioavailability and pharmacokinetics during repeated administration was investigated in six volunteers. The RIA method was adopted to measure plasma and urine levels. Acipimox was rapidly and almost completely absorbed after the three single doses. About 90% of the administered dose was recovered as unchanges drug in urine collected up to 24 h. Peak plasma levels, area under plasma levels curves and urinary excretion were linearly related to the administered dose. The presence of food in the gastro-intestinal tract did not adversely affect the bioavailability of the drug. No significant changes were noted in the rate of elimination after 6 days of treatment with 250 mg t.i.d. Plasma levels determined after the 19th dose were in good agreement with those predicted on the assumption of linear pharmacokinetics and a one-compartment open model, with a half-life of about 2 h.

Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects

“…Sporadic rebound lipolysis during treatment with acipimox over a comparable time period has previously been described (42,53) and may involve a desensitization to drug action (53) or be due to insufficient plasma levels (52) if metabolized quickly. Acipimox at the given dose exerts maximum efficacy 2 h after ingestion, and plasma concentrations tail off sharply thereafter (34). Corresponding nadirs in circulating FFA levels were seen 2 h after each tablet ingestion in our subjects.…”

Effect of the antilipolytic nicotinic acid analogue acipimox on whole-body and skeletal muscle glucose metabolism in patients with non-insulin-dependent diabetes mellitus.

“…Acipimox (5-methyl-pyrazine carboxylic acid 4-oxide, Farmitalia Carlo Erba, Milano, Italy) is a new potent and long-acting (8 h) antilipolytic drug, which has been derived from NA (14). By lowering plasma and possibly skeletal muscle concentrations of NEFA, Acipimox may have a potential beneficial effect on glucose metabolism in patients with NIDDM.…”

Increased affinity of LDL for their receptors after acipimox treatment in hypertriglyceridemia

“…In both competition and uptake-degradation experiments, acipimox treatment restored the LDL binding capacity. The improved binding does not depend upon the association of A with LDL, since the drug only binds to albumin in plasma [16].…”