Cyclosporin and tacrolimus increase plasma levels of adenosine in kidney transplanted patients

Abstract

The immunosuppressive agents, cyclosporin (CsA) and tacrolimus (FK506), display cardioprotective activities. The mechanism would consist on the inhibition of the enzyme, adenosine kinase (AK), leading to an increase in adenosine (ADO) levels. ADO, inosine (INO) and nucleotide plasma levels were measured in kidney transplant recipients before and 1, 2, 4, 6 and 8 h after the administration of CsA or FK506. After CsA and FK506 administration, ADO plasma levels significantly increased, reaching a peak level after 2 h (483 ± 124 and 429 ± 96 nm, respectively), and then progressively declined. Calculated peak values (tmax) of ADO were slightly delayed with respect to those of CsA and FK506. Treatment with rapamycin did not influence the phenomenon. The dynamic profile of plasma changes of ADO, nucleotides and INO were consistent with the inhibition of the enzyme, AK. ADO increase may be clinically relevant in terms of anti-ischaemic, tissue protecting, and immunosuppressive activities as well as in terms of nephrotoxicit

Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19

“…For example, the antiplatelet agents dipyridamole and dilazep, both inhibitors of ENT1 and ENT2 [ 58 ], have been reported to increase plasma adenosine levels by almost two-fold [ 59 ]. Other drugs with the ability to increase plasma adenosine levels include cyclosporin and tacrolimus [ 60 ].…”

The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases

“…In addition to the direct receptor-targeting ligands, increasing efforts have been focused on identifying novel pharmacological agents able to modulate the extracellular levels of endogenous purines through targeting catabolic enzymes, nucleoside transporters, and other release mechanisms (see Table 2). In addition, a number of anti-inflammatory agents currently used to treat IMIDs, such as cyclosporine (Neoral, Sandimmune, Gengraf), salicylates (aspirin), methotrexate (Trexall, Rasuvo, Otrexup), sulfasalazine (Azulfidine, Sulfazine, Azulfidine EN-tabs), and the novel JAK-STAT inhibitor tofacitinib (Xeljanz, Xeljanz XR) have been shown to exert their beneficial effects by increasing extracellular adenosine levels (Morabito et al, 1998;Cronstein et al, 1999;Capecchi et al, 2005;Cronstein, 2006b;Koizumi et al, 2015).…”