Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulationReport as inadecuate




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Osteoporosis International

, Volume 28, Issue 5, pp 1745–1752

First Online: 16 February 2017Received: 30 November 2016Accepted: 23 January 2017DOI: 10.1007-s00198-017-3941-3

Cite this article as: Bone, H.G., Walter, M.A., Hurley, M.E. et al. Osteoporos Int 2017 28: 1745. doi:10.1007-s00198-017-3941-3

Abstract

SummaryNo clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption.

IntroductionConcurrent treatment of osteoporosis with alendronate Aln and hypothyroidism with levothyroxine LT4 may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln Aln-NEF and LT4.

MethodsA randomized, open-label, 3-way crossover study was conducted in 30 healthy adults 15 women. Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone 70 mg, LT4 alone 600 μg, or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals CIs for the test-reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point AUC0-t and maximum concentration Cmax. Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently-Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently-LT4 alone.

ResultsGeometric mean ratios Aln-NEF with LT4-Aln-NEF alone were 0.927 90% CI 0.795–1.081 for AUC0–8 and 0.912 90% CI 0.773–1.077 for Cmax, demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios LT4 with Aln-NEF-LT4 alone were 1.049 90% CI 0.983–1.119 for AUC0–48 and 1.075 90% CI 1.006–1.148 for Cmax, demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated.

ConclusionsThere was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

KeywordsAlendronate Bisphosphonate Drug interaction Levothyroxine Pharmacokinetics 



Author: H. G. Bone - M. A. Walter - M. E. Hurley - S. Epstein

Source: https://link.springer.com/







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