title: Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.
abstract: 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.
  
  
  
  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.
  
  
  
  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 (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.
  
  
  
  Geometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795-1.081) for AUC0-8and 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 AUC0-48and 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.
  
  
  
  There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.
authors.affiliation: Michigan Bone & Mineral Clinic, 22201 Moross Road, Suite 260, Detroit, MI, 48236, USA. hgbone.md@att.net.
authors.forename: H G
authors.identifier: 0000-0002-4227-2595
authors.initials: HG
authors.lastname: Bone
authors.affiliation: Mission Pharmacal Company, 10999 Interstate Highway 10 West, Suite 1000, San Antonio, TX, 78230, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Walter
authors.affiliation: Hurley Consulting Associates Ltd., 25 DeForest Avenue, Summit, NJ, 07901, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Hurley
authors.affiliation: Division of Endocrinology Diabetes and Bone Disease, Icahn School of Medicine at Mt. Sinai, Atran Building, 1428 Madison Avenue, 4th Floor, Box 1055, New York, NY, 10029, USA.
authors.forename: S
authors.initials: S
authors.lastname: Epstein
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019386:Alendronate / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; 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 / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D055815:Young Adult
chemical_list: D050071:Bone Density Conservation Agents; D004338:Drug Combinations; D013974:Thyroxine; D019386:Alendronate
keywords: Alendronate; Bisphosphonate; Drug interaction; Levothyroxine; Pharmacokinetics