This study was conducted to investigate the pharmacologic interaction between EVR and TAC at the blood and pancreas level. Male Sprague-Dawley (SD) was administrated with TAC (6 mg/kg/day, P.O.) and EVR (1 or 2 mg/kg/day, P.O.) for 4 weeks. Pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT), plasma insulin concentrations, blood glucose level and HbA1c level. Level of each drug was evaluated in the whole blood and pancreas tissue using liquid chromatography-mass spectrometry. Level of 8-hydroxy-2-deoxyguanosin (8-OHdG) measured in serum. The TAC treatment induced pancreatic dysfunction compared with the VH group, but EVR treatment did not cause pancreatic dysfunction. But combination with TAC and EVR aggravated TAC-induced pancreatic injury. The AUGg level measured with IPGTT revealed that the TAC group was higher than that of VH group (620 ± 36 vs. 586 ± 28 mg/dL/min, p < 0.05 vs. VH). Level of insulin was lower in the TAC group compared to the VH group (0.33 ± 0.05 vs. 0.46 ± 0.03 ng/mL, p < 0.05 vs. VH). The HOMA-R index was higher in the TAC group than that of the VH group (7.12 ± 0.33 vs. 4.91 ± 0.23, P < 0.05 vs. VH). Addition of EVR on TAC showed aggravation of pancreatic islet dysfunction compare to the TAC group. In whole blood, higher TAC level was detected in the TAC+EVR groups than TAC group in a dose dependent manner. EVR level was also shown to similar pattern. In pancreas tissue, higher TAC level was detected in the TAC+EVR groups compare to the TAC group. Like TAC, the higher level of EVR in pancreas was also detected in the TAC + EVR groups compared with the EVR groups. 8-OHdG level in serum were significantly increased in the TAC group compared to the VH group. However, combination administration of EVR showed much higher 8-OHdG level than those of the TAC group. EVR aggravates TAC-induced pancreatic injury and pharmacologic interaction between EVR and TAC have synergy effect. This finding provides better understanding of the EVR when combined with the TAC treatment in organ transplant patient.
To cite this abstract in AMA style:Piao S, Lim S, Doh K, Jin L, Chung B, Heo S, Yang C. Everolimus Aggravates Tacrolimus-Induced Pancreatic Injury by Pharmacologic Interaction between Everolimus and Tacrolimus [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/everolimus-aggravates-tacrolimus-induced-pancreatic-injury-by-pharmacologic-interaction-between-everolimus-and-tacrolimus/. Accessed April 6, 2020.
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