Pharmacokinetics and Bioequivalence Evaluation of Two Acipimox Tablets: A Single-Dose, Randomized-Sequence, Two-Way Crossover Study in Healthy Chinese Male Volunteers

Abstract

Objective:

The study was designed to compare the pharmacokinetic parameters and relative bioavailability of a newly generic acipimox 250-mg tablets (test formulation) with a branded 250-mg tablets (reference formulation).

Methods:

A single-dose, randomized-sequence, 2-way crossover study was conducted in 20 healthy Chinese male volunteers in the fasted state. Plasma samples were collected over 12 h after a single oral dose of 250-mg acipimox test or reference, followed by a 7-day washout period. Plasma concentrations of acipimox were analyzed by high-performance liquid chromatography. Drug And Statistical-Version 2.0 was used to calculate the pharmacokinetic parameters and assess bioequivalence of the 2 formulations. It is considered bioequivalent if the 90% CIs of the mean ratios (test: reference) for C_max, AUC_0–t and AUC_0–∞ are all within the range from 80% to 125%.

Results:

No period, formulation, or sequence effects were observed on any pharmacokinetic parameters. The main pharmacokinetic parameters for the test and reference were as follows: t_1/2 were 1.412±0.168 h and 1.390±0.162 h; T_max were 1.850±0.462 h and 1.800±0.571 h; C_max were 4.035±1.055 μg · ml^-1 and 3.858±0.986 μg · ml^-1; AUC_0–12 were 14.006±2.564 μg · ml^-1 · h and 13.345±2.128 μg · ml^-1 · h, and the AUC_0–∞ were 14.147±2.568 μg · ml^-1 · h and 13.486±2.117 μg · ml^-1 · h. The 90% CIs for the ratios (test/reference) of C_max, AUC_0–12, and AUC_{0 − ∞} were 98.0–111.2%, 100.8–108.5%, and 100.8–108.3%, respectively.

Conclusions:

In this small study, a single 250-mg oral dose of an acipimox tablet (test formulation) is bioequivalent to the established reference formulation.

Key words

determination - acipimox - HPLC

• References

• 1 Sirtori CR, Gianfranceschi G, Sirtori M et al. Reduced triglyceridemia and increased high density lipoprotein cholesterol levels after treatment with acipimox, a new inhibitor of lipolysis. Atherosclerosis Feb-Mar 1981; 38: 267-271
• 2 Stirling C, McAleer M, Reckless JPD et al. Effects of acipimox, a nicotinic acid derivative, on lipolysis in human adipose tissue and on cholesterol synthesis in human jejunal mucosa. Clin Sci Jan 1985; 68: 83-84
• 3 Fuccella LM, Goldaniga GC, Lovisolo PP et al. Inhibition of lipolysis by nicotinic acid and by acipimox. Clin Pharmacol Ther Dec 1980; 28: 790-795
• 4 Taskinen MR, Nikkilä EA. Effects of acipimox on serumlipids, lipoproteins and lipolytic enzymes in hypertriglyleridemia. Atherosclorosis Feb 1988; 69: 249-255
• 5 Sirtori CR, Gianfranceschi G., Sirtori M et al. Reduced triglyceridemia and increased high density lipoprotein cholesterol levels after treatment with Acipimox, a new inhibitor of lipolysis. Atherosclorosis Feb-Mar 1981; 38: 267-271
• 6 Musatti L, Maggi E, Moro E et al. Bioavailability and pharmacokinetics in man of acipimox, a new antilipolytic and hypolipemic agent. Int Med Res 1981; 9: 381-386
• 7 Maggi E, Pianezzola E, Valzelli G.. Radioimmunoassay of acipimox in human plasma and urine. Pharmacol Res Commun Nov 1984; 16: 1081-1090
• 8 Efthymiopoulos C, Strolin Benedetti M, Poggesi I et al. Pharmacokinetics of acipimox and of its N-deoxy metabolite following single and repeated oral administration to healthy volunteers. Therapie Jan-Feb 1993; 48: 23-26
• 9 State Food and Drug Administration of People’s Republic of China. Guideline for bioavailability and bioequivalence studies of generic drug products [in Chinese]. http://www.cde.org.cn/zdyz.do?method=largePage&id=2066
• 10 European Medicines Agency (EMEA) Note for guidance on good clinical practice. ICH topic E 6 (R1) http://www.emea.europa.eu/pdfs/human/ich/013595en.pdf
• 11 State Food and Drug Administration of China. Guideline for Good Clinical Principles [in Chinese]. http://www.sda.gov.cn/WS01/CL0053/24473.html
• 12 Shin KC, Kwok CF, Hwu CM et al. Acipimox attenuates hypertriglyceridemia in dyslipidemic non-insulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control. Diabetes Research and Clinical Practice 1997; 36: 113-119