A comparison of the pharmacokinetics of two different formulations of extended-release niacin

ABSTRACT

Objective: The objective of this study was to compare pharmacokinetic parameters of niacin extended-release tablets (NER uncoated)^* and niacin extended-release caplet formation (NER coated)^†.

* Niaspan is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA

† Niaspan CF is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA

Research design and methods: Twenty-five healthy male and female subjects were enrolled in a four-period, open-label, randomized, crossover study. Both NER uncoated and NER coated were given as 1 × 1000 mg or 2 × 500 mg tablets. Similarity of NER coated 1 × 1000 mg and NER uncoated 2 × 500 mg was declared if 90% confidence intervals for the geometric mean ratio (GMR) for nicotinuric acid (NUA) C_max fell within the pre-specified bounds of [0.7, 1.43].

Results: The GMRs for NUA C_max demonstrated similarity in the pharmacokinetics of NER uncoated 2 × 500 mg, NER coated 1 × 1000 mg, and NER coated 2 × 500 mg. Although less stringent comparability bounds were prespecified for the primary pharmacokinetic endpoint (i.e., C_max of plasma NUA), inspection of the primary comparison of interest indicated that a hypothesis with more stringent bioequivalence bounds of [0.8, 1.25] would have been satisfied. The NUA C_max for NER uncoated 1 × 1000 mg was approximately 40% higher than that seen for the other three treatments. In contrast, total urinary excretion of niacin and its metabolites, an approximate measure of bioavailability, was similar for all four treatments.

Conclusion: The pharmacokinetic profile of the original NER uncoated formulation dosed as 2 × 500 mg was similar to the new film-coated formulation, NER coated, dosed as 1 × 1000 mg.

Key words: :

• Niacin
• Niacin extended-release
• Pharmacokinetics
• Nicotinuric acid

Acknowledgements

Declaration of interest: This study was sponsored by Merck & Co. The authors thank Amy O. Johnson-Levonas, Ph.D., and Adrian Harewood, M.D., of Merck for their expert assistance with preparing this manuscript for publication. B.L., K.R.,W.-L.L., L.W., J.F.P., J.W. and E.L. are employees of Merck and may own company stock. J.K. and K.R. are employees of MDS Pharma Services and contributed to the conduct of this study.

Notes

* Niaspan is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA

† Niaspan CF is a product manufactured by CF Kos Life Sciences LLC, Cranbury, NJ, USA