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Objective To study the calcium metabolism in tacrolimus(FK506)induced rats nephrotoxicity and the preventive effect of calcium channel blocker.Methods Twenty-four Spragueinduced or FK506-induced nephropathy model.Blood creatinine,blood electrolytes,renal tissue histopathology(HE stain)and the change of ultrastructural organization in renal cells by transmission electron microscope were observed.Results The blood creatinine levels of both CsA and FK506 groups [(36.00±2.61)and(34.17±4.54)μmol/L] were significantly higher than those of the FK506+Dilgroup and control group(all P＜0.05).The blood calcium levels of both CsA and FK506 groups (2.00±0.04 and 2.05±0.04 mmol/L) were significantly lower than those of the FK506+Dil group and control group(all P＜0.05).The blood creatinine and calcium levels of FK506+Dil group were not significantly different with those of control group(P＞O.05).Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells and intra-cellular mitochondria swelling and vacuolization in the CsA and FK506 groups.However,the pathological changes of the FK506+Dil group were remarkably milder in comparison with the CsA and FK506 groups.Concluum channel blocker,Dil,could prevent the FK506-induced nephrotoxicity.
ABSTRACT
Objective To study the clinical monitoring of tacrolimus (FK506) area under the curve (AUC) of concentration-time after the first oral dose in kidney transplant recipients. Methods Sixteen kidney transplant recipients were treated with anti-lymphocyte globulin (ALG) and methyprednisolone (MP) for 3 days after operation.Then FK506 capsules were given orally at the same dose,0.075 mg/kg,on the third day.The pharmacokinetic monitoring of FK506 were conducted as follows.FK506 concentrations were measured by ELISA at 0.5,1.0,1.5,2.0,3.0,5.0,8.0,12.0 hours after the first oral dose. The data of FK506 pharmacokinetics were calculated using 3P87 pharmacokinetic procedures and SPSS 8.0. Results AUC of concentration-time of the first dose ranged from 44.40 ?g?h -1 ?L -1 to 158.01 ?g?h -1 ?L -1 (mean, 92.23?34.97 ?g?h -1 ?L -1 ). The correlation between the first tacrolimus trough concentration (C min ) and AUC had statistic significance ( r=0.650,P