Effects of lysine clonixinate and ketorolac tromethamine on prostanoid release from various rat organs incubated ex vivo
| Autor: | Dirk Pallapies, G. Rohleder, P. Nagyiványi, D.-J. Atkins, A.Meyer zum Gottesberge, A. Salinger, Bernhard A. Peskar |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Indomethacin Administration Oral Prostaglandin 6-Ketoprostaglandin F1 alpha Pharmacology Dinoprost Kidney Ketorolac Tromethamine General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Oral administration Animals Potency Cyclooxygenase Inhibitors Rats Wistar Tolmetin Tromethamine General Pharmacology Toxicology and Pharmaceutics Lung Analgesics Dose-Response Relationship Drug biology Chemistry Lysine Anti-Inflammatory Agents Non-Steroidal Brain Prostanoid General Medicine Clonixin Rats Isoenzymes Thromboxane B2 body regions Drug Combinations Gastric Mucosa Prostaglandin-Endoperoxide Synthases Toxicity Prostaglandins biology.protein Cyclooxygenase Ex vivo |
| Zdroj: | Life Sciences. 57:83-89 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/0024-3205(95)00249-6 |
| Popis: | The release of prostanoids from rat brain, gastric mucosa, lungs and kidneys incubated ex vivo has been investigated for up to 5 h after oral administration of 10 mg / kg lysine clonixinate or 1 mg / kg ketorolac tromethamine. Additionally, 60 min after drug administration, a time point of near-maximal inhibition of prostanoid release, the effects of 2.5, 10 and 30 mg / kg lysine clonixinate and of 0.0225, 0.15 and 1 mg / kg ketorolac tromethamine were compared. In all organs investigated both drugs inhibited fatty acid cyclooxygenase (COX) in a dose-dependent manner, but ketorolac tromethamine was more potent and had a longer-lasting effect than lysine clonixinate. While the ID 50 values for lysine clonixinate were in the same order of magnitude for all 4 organs investigated, ketorolac tromethamine exhibited some organ selectivity with a particularly high activity in the kidneys. This effect might be related to the renal toxicity of ketorolac tromethamine. On the other hand, the difference in potency was smallest in brain suggesting that inhibition of central prostanoid biosynthesis could contribute to the rapid and effective inhibition of pain by both drugs. IC 50 values for inhibition of purified COX-1 and COX-2 in vitro were slightly lower for lysine clonixinate (2.4 and 24.6 μg / ml, respectively) than for ketorolac tromethamine (3.7 and 25.6 μg / ml, respectively). |
| Databáze: | OpenAIRE |
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