Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.
No 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.


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 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 (C max). 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.


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 C max, 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 C max, demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated.


CONCLUSIONS
There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.
['Bone|H G|HG|0000-0002-4227-2595', 'Walter|M A|MA|', 'Hurley|M E|ME|', 'Epstein|S|S|']
D000284:Administration, Oral D000293:Adolescent D000328:Adult D019386:Alendronate D050071:Bone Density Conservation Agents D018592:Cross-Over Studies D004334:Drug Administration Schedule D004338:Drug Combinations D004339:Drug Compounding D004347:Drug Interactions D005260:Female D064368:Healthy Volunteers D006801:Humans D008297:Male D008875:Middle Aged D013810:Therapeutic Equivalency D013974:Thyroxine D055815:Young Adult
Pharmacokinetics Levothyroxine Alendronate Bisphosphonate Drug interaction