Abstract Summary No clinically important pharmacokinetic interference ofalendronateoccurredbetweenaneweffervescentformulation of alendronate and levothyroxine when coadministered. The combinationdoesnotmateriallyaffectlevothyroxineabsorption. Introduction Concurrent 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. Methods A 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 plasmaAlnand serum LT4.Pharmacokineticdrug druginteraction 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 measureabletimepoint(AUC0-t)andmaximumconcentration (Cmax).Resultswerecomparedtothedefaultno-effectboundaries 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. Results Geometric 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%CI0.983–1.119) 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. Conclusions There was no clinically important pharmacokineticinterferencebetweentheAln-NEFformulationandLT4. Aln-NEF does not materially affect LT4 absorption.
Keywords Alendronate .Bisphosphonate .Druginteraction . Levothyroxine .Pharmacokinetics