Djabri Asma, van't Hoff William, Brock Penelope, Wong Ian C K, Guy Richard H, Delgado-Charro M Begoña
Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA1 7AY, UK.
Pharm Res. 2015 Feb;32(2):590-603. doi: 10.1007/s11095-014-1488-y. Epub 2014 Sep 5.
To explore the potential of non-invasive reverse iontophoresis transdermal extraction of iohexol as a marker of glomerular filtration rate.
A series of in vitro experiments were undertaken to establish the feasibility of iohexol reverse iontophoresis and to determine the optimal conditions for the approach. Subsequently, a pilot study in paediatric patients was performed to provide proof-of-concept.
The iontophoretic extraction fluxes of iohexol in vitro were proportional to the marker subdermal concentration and the reverse iontophoretic technique was able to track changes dynamically in simulated pharmacokinetic profiles. Reverse iontophoresis sampling was well tolerated by the four paediatric participants. The deduced values of the iohexol terminal elimination rate constant from transdermal reverse iontophoresis sampling agreed with those estimated by conventional blood sampling.
Reverse iontophoretic transdermal extraction fluxes mirrored the subdermal concentration profiles of iohexol, a relatively large neutral marker of glomerular filtration both in vitro and in vivo. The efficiency of extraction in vivo was well predicted by the in vitro model used.
探讨非侵入性反向离子电渗法经皮提取碘海醇作为肾小球滤过率标志物的潜力。
进行了一系列体外实验,以确定碘海醇反向离子电渗法的可行性并确定该方法的最佳条件。随后,在儿科患者中进行了一项初步研究以提供概念验证。
碘海醇在体外的离子电渗提取通量与皮下标志物浓度成正比,并且反向离子电渗技术能够动态跟踪模拟药代动力学曲线的变化。四名儿科参与者对反向离子电渗采样耐受性良好。经皮反向离子电渗采样得出的碘海醇终末消除速率常数与传统血液采样估计的值一致。
反向离子电渗经皮提取通量反映了碘海醇的皮下浓度曲线,碘海醇是一种在体外和体内均相对较大的肾小球滤过中性标志物。所使用的体外模型能够很好地预测体内提取效率。