Effect of Lipophilicity on in Vivo Iontophoretic Delivery.I. NSAIDs

概要

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The effect of drug lipophilicity on in vivo iontophoretic transdermal absorption was evaluated. Non-steroidal anti-inflammatory drugs(NSAIDs)were selected as model drugs with a wide range of lipophilicity : salicylic acid(SA), ketoprofen(KP), naproxen(XP)and indomethacin(IM). Cathodal iontophoresis of NSAIDs was conducted in rats(0.625mA/cm^2 ; 90min), and drug concentrations in skin, cutaneous vein and systemic vein were determined. Skin concentrations of NSAID were higher in the case of lipophilic(SA=KP=NP<IM), whereas cutaneous plasma concentrations decreased with an increase in lipophilicity(SA>KP=NP>IM). Additionally, the deoendence of drug lipophilicity on systemic plasma concentration was similar to cutaneous plasma concentration. The transfer rate from skin to cutaneous vein(R_<sc>)was calculated from the arterio-venous plasma concentration difference of drug in the skin. Normalized R_<sc> by skin concentration(R_<sc>/X_s)yielded a negative correlation with the logarithm of n-octanol/buffer partition coefficient(Log P at pH 7.4), suggesting that transfer of NSAIDs from skin to cutaneous vein decreased with inbreasing lipoohilicity(SA>KP=NP>}IM). This correlation means that drug partitioning between viable epidermis might be a dominant step.
公益社団法人日本薬学会の論文
2001-03-01