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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Warner, T. D. Giuliano, F. |
| Description | Author Affiliation: Giuliano F ( Vascular Inflammation, The William Harvey Research Institute, St. Bartholomew's and The Royal School of Medicine and Dentistry, London.) |
| Abstract | 1. In this study we describe experiments to establish ex vivo the selectivity of non-steroidal anti-inflammatory drugs (NSAIDs) given in vivo. 2. Anaesthetised (Inactin, 120 mg kg(-1)) male Wistar rats (220-250 g) received an i.v. dose of one of the following compounds (dose mg kg(-1)): aspirin (20), diclofenac (3), L-745,337 (30), nimesulide (15), salicylate (20), sulindac (10). Blood samples were taken before and up to 6 h after dosing and the plasma obtained from it was tested for its ability to inhibit prostanoid formation in IL-1beta-treated A549 cells (COX-2 system) and human washed platelets (COX-1 system). For control the same compounds were also added directly to the assay systems. 3. All drugs, except sodium salicylate, inhibited COX-1 and COX-2 when added directly to the test systems. Plasma from aspirin-treated rats was without effect on either COX-1 or COX-2, consistent with the rapid in vivo metabolism to salicylate. Conversely, plasma from sulindac-treated rats inhibited COX-1 and COX-2 with potencies according with in vivo metabolism to sulindac sulphide. Diclofenac was COX-1/2 non-selective when tested in vitro, but a slightly preferential inhibitor of COX-2 when tested ex vivo. Nimesulide was confirmed as preferential inhibitor of COX-2 both in vitro and ex vivo. L-745,337 was a selective COX-2 inhibitor when tested in vitro or ex vivo. 4. In conclusion, our experiments show clearly (a) NSAIDs inactivation, (b) activation of prodrugs, and (c) NSAIDs selectivity. Our assay provides useful information about the selectivity of NSAIDs that could be extended by the analysis of plasma samples taken from humans similarly treated with test drugs. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 8 |
| Volume Number | 126 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-04-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Anti-Inflammatory Agents, Non-Steroidal Pharmacology Cyclooxygenase Inhibitors Isoenzymes Metabolism Prostaglandin-Endoperoxide Synthases Analgesics Animals Aspirin Blood Platelets Drug Effects Enzymology Blood Pressure Carcinoma Cyclooxygenase 1 Cyclooxygenase 2 Cyclooxygenase 2 Inhibitors Diclofenac Dinoprostone Biosynthesis Blood Indans Membrane Proteins Rats, Wistar Salicylates Substrate Specificity Sulfonamides Sulindac Thromboxane B2 Tumor Cells, Cultured Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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