title: Comparison of the pharmacokinetics and tolerability of HCP1004 (a fixed-dose combination of naproxen and esomeprazole strontium) and VIMOVO® (a marketed fixed-dose combination of naproxen and esomeprazole magnesium) in healthy volunteers.
abstract: BACKGROUND
  HCP1004 is a newly developed fixed-dose combination of naproxen (500 mg) and esomeprazole strontium (20 mg) that is used in the treatment of rheumatic diseases and can reduce the risk of nonsteroidal anti-inflammatory drug-associated ulcers. The aim of this study was to evaluate the pharmacokinetics (PK) and safety of HCP1004 compared to VIMOVO(®) (a marketed fixed-dose combination of naproxen and esomeprazole magnesium).
  
  
  METHODS
  An open-label, randomized, two-treatment, two-sequence crossover, single-dose clinical study was conducted in 70 healthy volunteers. In each period, a reference (VIMOVO(®)) or test (HCP1004) drug was administered orally, and serial blood samples for PK analysis were collected up to 72 hours after dosing. To evaluate the PK profiles, the maximum plasma concentration (Cmax) and the area under the concentration-time curve from 0 to the last measurable time (AUC0-t) were estimated using a noncompartmental method. Safety profiles were evaluated throughout the study.
  
  
  RESULTS
  Sixty-six of the 70 subjects completed the study. The Cmax (mean ± standard deviation) and AUC0-t (mean ± standard deviation) for naproxen in HCP1004 were 61.67 ± 15.16 µg/mL and 1,206.52 ± 166.46 h · µg/mL, respectively; in VIMOVO(®); these values were 61.85 ± 14.54 µg/mL and 1,211.44 ± 170.01 h · µg/mL, respectively. The Cmax and AUC0-t for esomeprazole in HCP1004 were 658.21 ± 510.91 ng/mL and 1,109.11 ± 1,111.59 h · ng/mL, respectively; for VIMOVO(®), these values were 595.09 ± 364.23 ng/mL and 1,015.12 ± 952.98 h · ng/mL, respectively. The geometric mean ratios and 90% confidence intervals (CIs) (HCP1004 to VIMOVO(®)) of the Cmax and AUC0-t of naproxen were 0.99 (0.94-1.06) and 1.00 (0.98-1.01), respectively. For esomeprazole, the geometric mean ratios (90% CI) for the Cmax and AUC0-t were 0.99 (0.82-1.18) and 1.04 (0.91-1.18), respectively. The overall results of the safety assessment showed no clinically significant issues for either treatment.
  
  
  CONCLUSIONS
  The PK of HCP1004 500/20 mg was comparable to that of VIMOVO(®) 500/20 mg for both naproxen and esomeprazole after a single oral dose. Both drugs were well-tolerated without any safety issues.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: YoonJung
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: HyeKyung
authors.initials: H
authors.lastname: Han
authors.affiliation: Clinical Trials Center, Gachon University Gil Medical Center, Incheon, Republic of Korea.
authors.forename: Dongseong
authors.initials: D
authors.lastname: Shin
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors.forename: Kyoung Soo
authors.initials: KS
authors.lastname: Lim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004338:Drug Combinations; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D056910:Republic of Korea; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D054328:Proton Pump Inhibitors; D009288:Naproxen; D064098:Esomeprazole
keywords: comparative pharmacokinetics; drug development; naproxen/esomeprazole