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首页> 外文期刊>Transplantation Proceedings >A prospective cross-over study comparing the pharmacokinetics of cyclosporine A and its metabolites after oral versus short-time intravenous cyclosporine A administration in pre-heart transplant patients.
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A prospective cross-over study comparing the pharmacokinetics of cyclosporine A and its metabolites after oral versus short-time intravenous cyclosporine A administration in pre-heart transplant patients.

机译：一项前瞻性交叉研究比较了心脏移植前患者口服和短时静脉内注射环孢菌素A后环孢霉素A及其代谢产物的药代动力学。

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Sometimes intravenous administration of cyclosporine (CsA) is essential before oral administration is possible. There are only a few reports available on the interindividual variability of CsA metabolism and different metabolite pattern depending on intravenous versus oral administration of CsA in heart transplant (HTx) patients. For effective inhibition of calcineurin we used a short infusion reaching peak concentrations after 2 hours. In a prospective cross-over study we compared the pharmacokinetics of CsA and its metabolites after oral (2.0 mg/kg body weight) versus intravenous (0.7 mg/kg body weight; 2-hour infusion) CsA administration (single test dose) in 7 pre-HTx patients. The pharmacokinetic parameters of CsA and its metabolites were analyzed using high-pressure liquid chromatography. The pharmacokinetic parameter area under the concentration time curve (AUC(0-infinity)) of CsA after intravenous administration was significantly lower (2903 ng*h*mL(-1)) than that after oral administration (4344 ng*h*mL(-1); P=.01). Peak concentrations, time to peak concentration, and terminal elimination half life were not significantly different. Short-time infusion of CsA resulted in a significant decrease in the AUC of the metabolites AM1 (3-fold), AM9 (10-fold), and AM1c (3-fold). A 2-hour infusion of CsA is just as effective as oral administration and the reduced amount of metabolites is advantageous for the patient.
机译：有时在必须口服之前必须先静脉注射环孢素（CsA）。关于心脏移植（HTx）患者中CsA的静脉内或口服给药，有关CsA代谢的个体差异和不同的代谢产物类型的报道很少，这方面的报道很少。为了有效抑制钙调神经磷酸酶，我们使用了短时间输注，并在2小时后达到峰值浓度。在一项前瞻性交叉研究中，我们比较了口服（2.0 mg / kg体重）与静脉内（0.7 mg / kg体重; 2小时输注）CsA给药（单次试验剂量）后CsA及其代谢物的药代动力学[7] HTx前患者。使用高压液相色谱分析了CsA及其代谢物的药代动力学参数。静脉给药后CsA的浓度时间曲线下的药代动力学参数区域（AUC（0-无穷大））比口服给药后（2344 ng * h * mL（-1））要低得多（2903 ng * h * mL（-1））。 -1）; P = .01）。峰值浓度，达到峰值浓度的时间和末端消除半衰期没有显着差异。短时注入CsA会导致代谢物AM1（3倍），AM9（10倍）和AM1c（3倍）的AUC显着降低。 2小时的CsA输注与口服给药一样有效，并且代谢物量的减少对患者有利。

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