Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions.
Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions.
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大鼠同时口服给药后环孢素和西罗莫司的相对组织分布：药代动力学相互作用的证据。
DOI：
10.1097/00007691-199804000-00001
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发表时间：
1998
影响因子：
2.5
通讯作者：
B. Kahan
中科院分区：
文献类型：
--
作者：
K. Napoli;Mou;Stanislaw M. Stepkowski;B. Kahan
作者试图确定同时经口（PO）给予环孢素（CsA）和西罗莫司（SRL，雷帕霉素）对CsA和SRL在大鼠中组织分布的影响。每组4只成年雄性Wistar-Furth大鼠接受2.5、5.0或10.0 mg CsA/kg ×天给药14天。其他组的4只成年雄性Wistar-Furth大鼠以1：6.25的SRL与CsA重量比给药14天，SRL剂量为0.4、0.8或1.6 mg/kg x天。CsA和SRL的浓度在心脏，肠，肾，肝，肺，肌肉，脾和睾丸的匀浆中进行了比较，在全血（WB）。有一个大的，剂量依赖性的，独特的分布CsA大鼠组织中，如先前已被充分记录。在恒定的摩尔剂量比下，同时口服SRL使大鼠组织中CsA浓度增加约2倍，尽管SRL未改变CsA组织-WB分配系数。伴随口服CsA给药产生剂量依赖性增加SRL组织浓度和减少SRL组织-WB分配系数。两种药物联合给药时组织和WB浓度增加的原因可能是两种药物竞争肠道P-糖蛋白结合位点引起的吸收增加、代谢速率降低或尚未确定的消除机制。剂量依赖性和不变的CsA组织-WB分配系数表明，SRL不影响CsA之间的中央和组织室，即组织摄取或细胞内结合的平衡。改变值的SRL组织-WB分配系数表明，在所研究的条件下，CsA干扰中央和组织室之间的SRL的平衡。
The authors sought to determine the effect of concomitant peroral (PO) administration of cyclosporine (CsA) and sirolimus (SRL, rapamycin) on the tissue distributions of CsA and SRL in the rat. Groups of four adult male Wistar-Furth rats were treated for 14 days with 2.5, 5.0, or 10.0 mg CsA/kg x day. Other groups of four adult male Wistar-Furth rats were treated for 14 days with a 1-to-6.25 weight-to-weight ratio of SRL to CsA at SRL doses of 0.4, 0.8, or 1.6 mg/kg x day. Concentrations of CsA and SRL in homogenates of heart, intestinal, kidney, liver, lung, muscle, spleen, and testes were compared to those in whole blood (WB). There was a large, dose-dependent, distinctive distribution of CsA among rat tissues, as has previously been well documented. At a constant molar dose ratio, concomitant oral administration of SRL produced an approximately two-fold increase in the concentrations of CsA in rat tissues, although SRL did not change the CsA tissue-to-WB partition coefficients. Concomitant oral CsA administration produced dose-dependent increases in SRL tissue concentrations and decreases in the SRL tissue-to-WB partition coefficients. The increases in tissue and WB concentrations on coadministration of both agents may be explained either by an increase in absorption caused by competition between the two agents for binding sites on P-glycoprotein in the gut, a reduced rate of metabolism, or to an as yet unidentified elimination mechanism. The dose-independent and unchanged CsA tissue-to-WB partition coefficients suggest that SRL does not affect the equilibrium of CsA between the central and tissue compartments, namely the tissue uptake or intracellular binding. Altered values of the SRL tissue-to-WB partition coefficients suggest that, under the conditions studied, CsA disturbs the equilibrium of SRL between the central and tissue compartments.
口服西罗莫司和环孢素之间的药代动力学相互作用对协同延长大鼠同种异体心脏移植存活的影响。
影响因子：
6.2
作者：
Stepkowski,SM;Napoli,KL;Wang,ME;Qu,X;Chou,TC;Kahan,BD
通讯作者：
Kahan,BD
影响因子：
19.6
作者：
Murgia, MG;Jordan, S;Kahan, BD
通讯作者：
Kahan, BD
影响因子：
15.9
作者：
KOLARS, JC;SCHMIEDLINREN, P;WATKINS, PB
通讯作者：
WATKINS, PB