Predictability of the clinical potency of NSAIDs from the preclinical pharmacodynamics in rats

Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]
A MukherjeeR Stein

Abstract

Relevance of the preclinical pharmacodynamic, toxicity and pharmacokinetic parameters predicting the clinical potency of nonsteroidal antiinflammatory drugs (NSAIDs) was evaluated. Data for oral potencies of 24 NSAIDs in rats were collected from the literature and from New Drug Applications with respect to the following parameters: antiinflammatory, analgesic, antipyretic, acute ulcerogenic activities, acute toxicity, in vitro inhibition of prostaglandin synthesis, acid dissociation constant (pKa), octanol-water partition coefficient and elimination half-life. Data for most of the in vivo parameters in rats were collected following single dose administration with the exception of adjuvant arthritis. Single and daily clinical doses were considered. All of these NSAIDs have been approved for marketing although not all have been sold in the USA. The preclinical data were compared to human dose (unit or daily doses) using single and multiple stepwise regression analyses. Analyses suggest that NSAIDs are effective in all models of preclinical tests for fever, pain and inflammation, however, carrageenin-induced rat paw edema model is clearly the best predictor of human dose. Rank order of preclinical models for predicting human dose ...Continue Reading

References

Jan 1, 1978·Scandinavian Journal of Rheumatology. Supplement·R MenasséR Jaques
Nov 1, 1978·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P C RisdallB Marchant
Jan 1, 1979·Journal of the American Academy of Child Psychiatry·C A Malone
Apr 1, 1992·Biopharmaceutics & Drug Disposition·J H Satterwhite, F D Boudinot
Jun 13, 1991·The New England Journal of Medicine·P M Brooks, R O Day
Dec 1, 1990·Chemical & Pharmaceutical Bulletin·T HatanakaY Morimoto
Apr 10, 1990·European Journal of Pharmacology·R A FerrariD R Haubrich
Feb 1, 1989·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·K KuriyamaS Hanada
Jan 1, 1986·Journal of Reproduction and Fertility·W Löscher, D Blazaki
Mar 1, 1987·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H W Ruelius
Mar 1, 1985·Annals of the Rheumatic Diseases·B Pal, M A Hossain
Jun 1, 1985·Arthritis and Rheumatism·C BaumM B Forbes
May 1, 1974·The American Journal of Digestive Diseases·P W DodgeS Tekeli
May 1, 1983·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·W KrauseE Schillinger
Mar 30, 1960·Annals of the New York Academy of Sciences·J J BURNSB B BRODIE
Dec 1, 1959·The Journal of Pharmacy and Pharmacology·M J SMITH
Dec 1, 1962·Proceedings of the Society for Experimental Biology and Medicine·C A WINTERG W NUSS
Aug 1, 1963·British Journal of Pharmacology and Chemotherapy·B B NEWBOULD
Mar 1, 1983·Pharmacotherapy·T Y Shen
Mar 1, 1983·Pharmacotherapy·Richard O Davies

❮ Previous
Next ❯

Citations

Nov 13, 2012·Critical Reviews in Biomedical Engineering·Hoi-Kei LonWilliam J Jusko
Jan 19, 2000·Proceedings of the National Academy of Sciences of the United States of America·A S KalgutkarL J Marnett
Sep 8, 2010·Journal of Pharmaceutical Sciences·James M Butler, Jennifer B Dressman
Sep 19, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Takaaki Komatsu, Tsukasa Sakurada
Jan 19, 2005·British Journal of Pharmacology·Ronald EsserPaul J Marshall
Jan 24, 2009·Journal of Veterinary Pharmacology and Therapeutics·J N KingP Lees
Jan 24, 2009·Journal of Veterinary Pharmacology and Therapeutics·J M GiraudelP Lees
Jul 13, 2011·Biochemical Pharmacology·Junko ImanishiSeitaro Mutoh
Jun 22, 2016·Inflammopharmacology·Taíssa Iolanda Checón FradeJanetti Nogueira de Francischi
Feb 20, 2007·Journal of Medicinal Chemistry·Katherine L LeeJohn C McKew

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.