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Evidence of NSAID partitioning into splanchnic lymphatics: Possible route to avoid first‐pass hepatic metabolism
Author(s) -
Lichtenberger Lenard Michael,
Phan Tri,
Dial Elizabeth
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1093.12
Subject(s) - aspirin , lymph , bioavailability , medicine , lymphatic system , pharmacology , splanchnic , anesthesia , hemodynamics , pathology
Aspirin and related NSAIDs rapidly undergo hydrolysis in blood and first‐pass hepatic metabolism. To better understand aspirin bioavailability in rodents we investigated whether a significant fraction of the drug may directly partition into the splanchnic lymphatics to promote NSAID circulatory half‐life and activity. Methods Fasted male Sprague Dawley rats, some of which were orally pretreated 0.5, 1 and 5 hrs earlier with aspirin (pulverized Immediate‐release Walgreens OTC aspirin in water at doses of 40 and 100 mg/kg), were placed under isoflurane anesthesia and after laparotomy the splachnic lymphatic was cannulated and lymph collected for the subsequent 60–120 min. At euthanasia, blood was also collected. Samples of lymph and blood were analyzed for the presence of salicylic acid (SA) and platelet thromboxane (TxB2) conc, using established colorimetiric and RIA procedures. Results We determined that lymph SA conc increased in a time‐ and dose‐dependent fashion after oral administration of aspirin and represented ~60% of circulating SA levels (using the 1 hr time point). Furthermore, aspirin dosing inhibited both lymph and plasma TxB2 conc by >;80%, 5hrs post‐treatment. Conclusion A significant fraction of intragastrically administered aspirin partitions into the lymphatic circulation in rats, which may be a critical factor in assuring the drug's bioavailability and therapeutic activity.