Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation

• Published in: Osteoporosis international Vol. 28; no. 5; pp. 1745 - 1752
• Main Authors: Bone, H. G., Walter, M. A., Hurley, M. E., Epstein, S.
• Format: Journal Article
• Language: English
• Published: London Springer London 01.05.2017; Springer Nature B.V
• Subjects: Administration, Oral; Adolescent; Adult; Alendronate - administration & dosage; Alendronate - adverse effects; Alendronate - blood; Alendronic acid; Bioavailability; Bisphosphonates; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - adverse effects; Bone Density Conservation Agents - blood; Cross-Over Studies; Drug Administration Schedule; Drug Combinations; Drug Compounding; Drug dosages; Drug interaction; Drug Interactions; Endocrinology; Esophagus; FDA approval; Female; Food; Healthy Volunteers; Humans; Hypothyroidism; Male; Medicine; Medicine & Public Health; Metabolism; Middle Aged; Older people; Original; Original Article; Orthopedics; Osteoporosis; Pharmacokinetics; Prescription drugs; Rheumatology; Sodium; Therapeutic Equivalency; Thyroid gland; Thyroxine; Thyroxine - administration & dosage; Thyroxine - adverse effects; Thyroxine - blood; Young Adult; Levothyroxine; Bisphosphonate; Drug interaction; Alendronate; Pharmacokinetics
• ISSN: 0937-941X; 1433-2965
• DOI: 10.1007/s00198-017-3941-3

Summary 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 (AUC 0- 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 AUC 0–8 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 AUC 0–48 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.