Distinct inhibitory effects of tacrolimus and cyclosporin a on calcineurin phosphatase activity

The Journal of Pharmacology and Experimental Therapeutics
Masahide FukudoKen-Ichi Inui

Abstract

We have compared the pharmacodynamic properties of calcineurin inhibitors tacrolimus and cyclosporin A in rats to clarify the different therapeutic drug monitoring strategy of both drugs in a clinical situation. In various tissue extracts, the inhibition of calcineurin activity by cyclosporin A was significantly greater than that by tacrolimus at the same drug concentration (1 microM) in the thymus, heart, liver, spleen, kidney, and testis (p < 0.05). The time profiles of blood concentrations and calcineurin activity in whole blood were examined after single or repeated administration of each drug in rats. A substantial time delay in the inhibition was observed following the single administration of tacrolimus or cyclosporin A, resulting in an anticlockwise hysteresis in the relationship between blood concentrations and calcineurin inhibition in whole blood. In contrast, such a hysteresis loop diminished after the repeated administration of each drug, and the recovery rate of calcineurin activity was greater for the inhibition induced by cyclosporin A than by tacrolimus. Furthermore, tacrolimus produced a comparable inhibition of calcineurin activity in whole blood at lower blood concentrations than cyclosporin A. Overall, the ...Continue Reading

References

Mar 1, 1979·Clinical Pharmacology and Therapeutics·L B SheinerJ Ham
May 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·D A FrumanS J Burakoff
Nov 2, 1984·Science·R E HandschumacherD W Speicher
Oct 1, 1984·Journal of Clinical Pathology·K AtkinsonJ Biggs
Sep 1, 1995·The Journal of Clinical Investigation·T D BatiukP F Halloran
Apr 1, 1996·Methods : a Companion to Methods in Enzymology·D A FrumanB E Bierer
Oct 6, 1997·The Journal of Clinical Investigation·T D BatiukP F Halloran
Nov 26, 1999·Transplantation·P F HalloranJ Noujaim
Oct 4, 2000·Physiological Reviews·F Rusnak, P Mertz
Jan 17, 2002·Transplantation·Steffen PelzlCaner Süsal
Jul 9, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·L KungP F Halloran
Jul 9, 2002·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Pernille B Koefoed-NielsenKaj A Jørgensen
Dec 14, 2002·Analytical Biochemistry·Benoît BlanchetAlain Astier
Jul 13, 2004·Clinical Pharmacokinetics·Christine E Staatz, Susan E Tett

❮ Previous
Next ❯

Citations

Feb 6, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Bente JespersenBoye L Jensen
Jul 3, 2007·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Masahide Fukudo
Dec 20, 2014·Biomarkers in Medicine·Mangalee FernandoZoltan H Endre
May 25, 2007·Neurobiology of Learning and Memory·Kelly T DineleyGiulio Taglialatela
Jun 9, 2006·Pharmacology & Therapeutics·Satohiro Masuda, Ken-ichi Inui
Oct 19, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Orla MaguireHans Minderman
Dec 23, 2015·Korean Journal of Hepato-biliary-pancreatic Surgery·Eunkyoung JwaSung-Gyu Lee
Jan 5, 2007·Biological & Pharmaceutical Bulletin·Shigeo ShinodaYoko Ohe
Feb 11, 2018·Scientific Reports·Lakmini Kumari SenavirathnaLin Liu
Dec 17, 2009·Therapeutic Drug Monitoring·Huub H van RossumJohannes van Pelt
Feb 19, 2010·American Journal of Physiology. Cell Physiology·Martin VossOtto Baumann
Jan 17, 2020·The FEBS Journal·Hema Bye-A-JeeUNKNOWN UniProt Consortium
Jan 19, 2013·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoshiteru TanakaMasayuki Nadai
Dec 14, 2011·Experimental Dermatology·Christiane KuschalSteffen Emmert

❮ 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.