Taljanski W, Pierzynowski S G, Lundin P D, Westrom B R, Eirefelt S, Podlesny J, Dahlback M, Siwinska-Golebiowska H, Karlsson B W
Department of Immunology, National Research Institute of Mother and Child, Warsaw, Poland.
Drug Metab Dispos. 1997 Aug;25(8):917-20.
The delivery and pharmacokinetics of cyclosporine A (CyA) given locally to the airways or iv was evaluated in young and adult rats. After intratracheal (i.t.) instillation of saline suspended CyA to adult rats, the CyA plasma levels peaked at 30 min with a bioavailability of 78.1 +/- 6.9%. After the i.t. instillation of CyA with micelles forming surfactant, Cremophor EL, in adult and young rats, the plasma levels peaked at 5 min with a bioavailability of 77.5 +/- 7.2% and 66.3 +/- 4.5%, respectively. The bioavailability of aerosolized CyA was 80.1 +/- 4.1% in adults. Thus, CyA is absorbed by the lungs into the systemic circulation of the rat in high amounts, independent of age and type of delivery system. Long-term treatment with i.t. instillations did not affect body weight gain in young and adult rats, and no histopathological changes were found in the lungs. It is important to emphasize that CyA plasma clearance in young rats was lower and elimination half-life longer than in adults. The slow elimination of CyA in young rats indicated profound pharmacokinetic age differences for this species.
在幼年和成年大鼠中评估了局部给予气道或静脉注射环孢素A（CyA）后的给药情况及药代动力学。对成年大鼠气管内（i.t.）滴注盐水悬浮的CyA后，CyA血浆水平在30分钟时达到峰值，生物利用度为78.1±6.9%。在成年和幼年大鼠中气管内滴注含形成胶束表面活性剂聚氧乙烯蓖麻油（Cremophor EL）的CyA后，血浆水平分别在5分钟时达到峰值，生物利用度分别为77.5±7.2%和66.3±4.5%。雾化CyA在成年大鼠中的生物利用度为80.1±4.1%。因此，CyA可被大鼠肺部大量吸收进入体循环，与年龄和给药系统类型无关。长期气管内滴注治疗不影响幼年和成年大鼠的体重增加，且肺部未发现组织病理学变化。需要强调的是，幼年大鼠的CyA血浆清除率低于成年大鼠，消除半衰期长于成年大鼠。幼年大鼠中CyA的缓慢消除表明该物种存在明显的药代动力学年龄差异。
