IPDAS: a novel technology brings new benefits when applied to naproxen sodium.
The Intestinal Protective Drug Absorption System (IPDAS) is a new oral drug delivery approach that is applicable to gastrointestinal (GI) irritant drugs, including the nonsteroidal anti-inflammatory drug (NSAID) class. Although naproxen, as the free acid or the sodium salt, has pharmacokinetic characteristics that are consistent with once-daily dosing, the GI irritant and ulcerogenic potential associated with a large bolus dose of naproxen precludes safe use of an immediate-release form. In addition, the desired pharmacodynamic activity of a once-daily dosage form of naproxen requires rapidly available naproxen for a prompt onset of analgesic activity, as well as a prolonged phase of absorption to provide 24-hour analgesic/anti-inflammatory activity. Naprelan (naproxen sodium; Wyeth-Ayerst Laboratories, Philadelphia, Pennsylvania) controlled-release tablets are a unique dosage form designed to achieve the desired features of such a once-daily presentation. Through a series of in vivo studies, the pharmaceutical design features of the product have been confirmed in humans using a combination of imaging and pharmacokinetic characterization. In addition, the potential for limiting any undesirable GI adverse events has been supported by evaluation of the GI toxicity of Naprelan in specialized animal toxicity studies. Naprelan exhibited in vivo performance characteristics that support the hypothesis that, as a once-daily dosage form, it may demonstrate safety and efficacy advantages in clinical evaluation.
Devane
J G
JG
Elan Corporation, Athlone, Ireland.
Butler
J
J
Mulligan
S
S
D000293:Adolescent; D000328:Adult; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D003692:Delayed-Action Preparations; D004064:Digestive System; D004285:Dogs; D016503:Drug Delivery Systems; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D009288:Naproxen / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity; D013552:Swine; D013556:Swine, Miniature
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D009288:Naproxen