title: Bioavailability of aspirin in rats comparing the drug's uptake into gastrointestinal tissue and vascular and lymphatic systems: implications on aspirin's chemopreventive action.
abstract: Aspirin is an effective analgesic and antiplatelet drug that in addition to its ability to reduce pain, inflammation and fever, appears to have efficacy in the prevention/treatment of a range of diseases including heart disease, numerous cancers and Alzheimer's. It is important to understand the bioavailability of aspirin and its major metabolite, salicylic acid, since dosage and route of administration can vary for treating differing diseases, and the major side-effects of aspirin, upper gastrointestinal ulceration and bleeding, are dose-dependent. We examined the time course for gastroduodenal uptake of aspirin and the appearance of its major metabolite salicylic acid in blood and lymph after intragastric (to simulate oral) and intraduodenal (to simulate enteric-coating) dosing in rats. Results show that after intragastric dosing, intact aspirin is absorbed primarily by the gastric mucosa and to a lesser extent by the duodenal mucosa. When aspirin is dosed intragastrically or intraduodenally, a much greater concentration of aspirin enters the lymph than the blood. In contrast, the concentration of salicylic acid was higher in blood than in lymph. Lymph levels of both aspirin and salicylic acid were sufficiently high so as to perform a pharmacologic function there, possibly as a chemopreventive agent against colon cancer and potentially the metastatic spread of non-gastrointestinal cancers.
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA. lenard.m.lichtenberger@uth.tmc.edu.
authors.forename: L M
authors.initials: LM
authors.lastname: Lichtenberger
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Phan
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Fang
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: S
authors.initials: S
authors.lastname: Edler
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: J
authors.initials: J
authors.lastname: Philip
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: T
authors.initials: T
authors.lastname: Li-Geng
authors.affiliation: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston - McGovern Medical School, Houston, TX, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Dial
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001241:Aspirin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001682:Biological Availability; D004333:Drug Administration Routes; D007413:Intestinal Mucosa / Q000378:metabolism*; D008208:Lymphatic System / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D020156:Salicylic Acid; D001241:Aspirin