Etoricoxib (antiarthritic, analgesic) (49-52)
Country of Origin : USA Originator: Merck & Co
First Introduction : Mexico Introduced by : Merck & Co Trade Name: Arcoxia CAS Registry No : 202409-33-4 Molecular Weight: 358.85
Etoricoxib is a COX-2 inhibitor developed as a follow-up of rofecoxib for the treatment of osteoarthritis, rheumatoid arthritis, dysmenorrhoea, gout, ankylosing spondylitis and pain. Several processes describe the preparation of etoricoxib in 4 or 5 steps from 6-methylnicotinate. The key step is the novel pyridine construction using annulation of a ketosulfone with a vinamidinium synthon. In human whole blood, in vitro, the IC50 value obtained for inhibition of COX-2 is 1.1 |nM as compared to 116 nM obtained for inhibition of COX-1. Thus, etoricoxib is the most selective COX-2 inhibitor to date, with a COX-1/COX-2 ratio of IC50 values of 106 for etoricoxib as compared to 35, 30, 7.6 for rofecoxib, valdecoxib and celecoxlb, respectively. Its in vivo potency is generally comparable to that of rofecoxib in animal models against inflammation (carrageenan-induced paw edema), pyrexia (LPS-induced pyresis), pain (carrageenan-induced hyperalgesia) and arthritis (adjuvant-induced arthritis). Etoricoxib is well tolerated with dose-proportional pharmacokinetics. It has no effect on bleeding time or platelet aggregation. The gastrointestinal tolerability of etoricoxib is excellent as demonstrated by [Cr] models of excretion in rats and squirrel monkeys. Moreover, etoricoxib, unlike naproxen is not associated with significant inhibition of gastric mucosal PGE2 synthesis compared to placebo. Etoricoxib is highly absorbed, has a W of 1.5 h and a half-life time of approximately 15 - 22 h. Five metabolites, weak inhibitors of COX-1 and COX-2 have been identified after renal excretion. Finally, although multiple CYP enzymes are involved in the metabolism of etoricoxib (CYP3A4 being the major contributor), etoricoxib is not a potent CYP3A4 inhibitor or inducer. In patients undergoing molar extraction, etoricoxib showed similar efficacy to naproxen sodium with a longer duration of analgesia than acetaminophen/codeine (approximately >24 h, 22 h and 5.2 h, respectively) and a better total pain relief score over 8 h. Similar efficacy of etoricoxib and naproxen was also seen in patients suffering of osteoarthritis. In the treatment of rtieumatoid arthritis and ankylosing spondylitis, etoricoxib demonstrated significantly superior efficacy compared to naproxen and placebo. Etoricoxib did not affect the pharmacokinetics of prednisolone (i.v. or p.o.) and its co-administration with antacids showed insignificant effects on the maximal concentration and its absorption.
Ezetimibe (hypolipidemic) (53-59)
Country of Origin : USA
First Introduction : Germany
Introduced by: Merck
Trade Name : Ezetrol
CAS Registry No : 163222-33-1
Molecular Weight: 409.44
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