title: Pharmacokinetics and relative bioavailability of a fixed-dose combination of enteric-coated naproxen and non-enteric-coated esomeprazole magnesium.
abstract: This randomized, 4-way crossover study assessed the single-dose pharmacokinetics and relative bioavailability of naproxen and esomeprazole after administration of a fixed-dose combination tablet of enteric-coated (EC) naproxen 500 mg and non-EC esomeprazole magnesium 20 mg (NAP/ESO tablet). Equivalent doses of an EC naproxen tablet plus an EC esomeprazole magnesium capsule taken concomitantly, an EC naproxen tablet alone, or an EC esomeprazole magnesium capsule alone were used as comparators. Forty healthy adults were randomized to receive 4 study treatments with a washout interval ≥12 days. Naproxen plasma profiles were similar between the NAP/ESO tablet and EC naproxen, although median t(max) was longest for the NAP/ESO tablet (5.3 vs 3.5-4.0 hours). Naproxen C(max), AUC(0-∞), and AUC(0-t) showed bioequivalence between naproxen formulations. The NAP/ESO tablet produced much shorter esomeprazole t(max) than the EC esomeprazole formulation (0.45 vs 2.5 hours). Esomeprazole C(max) and AUCs were comparable between the EC esomeprazole formulation administered with or without EC naproxen but were lower with the NAP/ESO tablet. In conclusion, there are no pharmacokinetic drug interactions between naproxen and esomeprazole. The NAP/ESO tablet is bioequivalent to EC naproxen, and as expected, the bioavailability of non-EC esomeprazole from the NAP/ESO tablet is lower than the EC esomeprazole formulation.
authors.affiliation: AstraZeneca Pharmaceuticals, Wilmington, DE 19850-5437, USA
authors.forename: Laurene
authors.initials: L
authors.lastname: Wang-Smith
authors.forename: John
authors.initials: J
authors.lastname: Fort
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Mark
authors.initials: M
authors.lastname: Sostek
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004338:Drug Combinations; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D010437:Peptic Ulcer / Q000139:chemically induced / Q000517:prevention & control; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D013608:Tablets, Enteric-Coated; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004338:Drug Combinations; D054328:Proton Pump Inhibitors; D013608:Tablets, Enteric-Coated; D009288:Naproxen; D064098:Esomeprazole