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首页> 外文期刊>Journal of pharmaceutical sciences. >Pharmacokinetics and pharmacodynamics analysis of transdermal iontophoresis of 5-OH-DPAT in rats: In vitro-in vivo correlation.
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Pharmacokinetics and pharmacodynamics analysis of transdermal iontophoresis of 5-OH-DPAT in rats: In vitro-in vivo correlation.

机译：5-OH-DPAT在大鼠体内的透皮离子电渗疗法的药代动力学和药效学分析：体内外相关性。

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摘要

Pharmacokinetics and dopaminergic effect of dopamine agonist 5-OH-DPAT in vivo were determined following transdermal iontophoresis in rats based on drug concentration in plasma (C(p)) and dopamine levels in striatum (C(DA)). Correlation of the in vitro transport with the pharmacokinetic-pharmacodynamic (PK-PD) profiles was characterized in the transport in dermatomed rat skin (DRS) and rat stratum corneum (RSC). The integrated in vivo PK-PD and in vitro transport models successfully described time course of C(p), C(DA), and in vitro flux in DRS and RSC. Population value of steady-state flux (J(ss)) in vivo (31 nmol/cm(2) . h with 95% confidence interval (CI) = 20-41) is closer to J(ss) in vitro in DRS (61 nmol/cm(2) . h, CI = 54-67) than in vitro J(ss) in RSC (98 nmol/cm(2) . h, CI = 79-117). On the other hand, skin release rate constant (K(R)) in vivo was similar to the K(R) in RSC (4.8/h, CI = 2.4-7.1 vs. 2.6/h, CI = 2.5-2.6). Kinetic lag time (t(L)) in vivo was negligible, which is close to in vitrot(L) in RSC (0.0 h, CI = 0.0-0.1). Based on nonlinear mixed-effect modeling, profiles of C(p) and C(DA) were successfully predicted using in vitro values of J(ss) in DRS with K(R) and t(L) in RSC. A considerable dopaminergic effect was achieved, indicating the feasibility to reach therapeutically effective concentrations of 5-OH-DPAT upon transdermal iontophoresis. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95: 1570-1585, 2006.
机译：根据血浆中的药物浓度（C（p））和纹状体中的多巴胺水平（C（DA）），在大鼠中进行透皮离子电渗疗法后，确定了多巴胺激动剂5-OH-DPAT在体内的药代动力学和多巴胺能作用。体外运输与药代动力学-药效学（PK-PD）分布的相关性以在皮肤切开的大鼠皮肤（DRS）和大鼠角质层（RSC）中的运输为特征。集成的体内PK-PD和体外运输模型成功描述了C（p），C（DA）的时程以及DRS和RSC中的体外通量。在DRS中，体内稳态通量（J（ss））的种群值（31 nmol / cm（2）。h，95％置信区间（CI）= 20-41）更接近J（ss）。比RSC中的体外J（ss）高61 nmol / cm（2）.h，CI = 54-67）（98 nmol / cm（2）.h，CI = 79-117）。另一方面，体内皮肤释放速率常数（K（R））与RSC中的K（R）相似（4.8 / h，CI = 2.4-7.1与2.6 / h，CI = 2.5-2.6）。体内的动力学滞后时间（t（L））可以忽略不计，这与RSC中的体外（L）接近（0.0 h，CI = 0.0-0.1）。基于非线性混合效应模型，使用DRS中的J（ss）和RSC中的t（L）的体外值成功预测了C（p）和C（DA）的分布。达到了明显的多巴胺能作用，表明在经皮离子电渗疗法上达到治疗有效浓度的5-OH-DPAT的可行性。 （c）2006 Wiley-Liss，Inc.和美国药剂师协会J Pharm Sci 95：1570-1585，2006。

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