caa a22 4500 477125514 CHVBK 20180405111648.0 cr unu---uuuuu 170330e19970101xx s 000 0 eng 10.1023/A:1012003416968 doi (NATIONALLICENCE)springer-10.1023/A:1012003416968 In Vivo Evaluation of Acyclovir Prodrug Penetration and Metabolism Through Rat Skin Using a Diffusion/Bioconversion Model [Elektronische Daten] [Hiroto Bando, Mikiko Sahashi, Fumiyoshi Yamashita, Yoshinobu Takakura, Mitsuru Hashida] Purpose. In order to evaluate the in vivo penetration of prodrugs which undergo metabolism in skin, we analyzed thein vivo penetration profiles of acyclovir prodrugs based on a two-layer skin diffusion model in consideration of metabolic process. Methods. Acyclovir prodrugs (e.g., valerate, isovalerate and pivarate) were used as model prodrugs and the amounts excreted in urine were measured after percutaneous application. In vivo penetration profiles were then estimated by employing a deconvolution method and the penetration of acyclovir prodrugs was analyzed using a diffusion model. Subsequently, diffusion, partitioning and metabolic parameters were compared under in vitro and in vivo conditions. Results. Although total penetration amounts at the end of the experiment were similar for the three prodrugs, the ratio of intact prodrug to total penetration amount differed significantly. Moreover, the excretion and absorption profiles were also very different for each prodrug. Enzymatic hydrolysis rate constants calculated under in vivo conditions were considerably larger than those obtained in the skin homogenate and in vitro penetration experiments. Conclusions. The present skin diffusion/bioconversion model combined with computer analysis enables us to comprehensively account for diffusion, partitioning and metabolism during in vivo percutaneous absorption. Nevertheless, different enzymatic hydrolysis rate constants obtained under bothin vivo and in vitro conditions demonstrate the difficulty of obtaining accurate values for in vivo enzymatic activity from related in vitro experiments. Plenum Publishing Corporation, 1997 in vivo skin penetration nationallicence acyclovir prodrug nationallicence diffusion/ bioconversion model nationallicence deconvolution nationallicence Bando Hiroto Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut Sahashi Mikiko Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut Yamashita Fumiyoshi Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut Takakura Yoshinobu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut Hashida Mitsuru Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 56-62 0724-8741 14:1<56 1997 14 11095 https://doi.org/10.1023/A:1012003416968 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012003416968 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bando Hiroto Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Sahashi Mikiko Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Yamashita Fumiyoshi Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Takakura Yoshinobu Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 700 1- Hashida Mitsuru Department of Drug Delivery Research, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshidashimoadachi-cho, Sakyo-ku, 606-01, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/1(1997-01-01), 56-62 0724-8741 14:1<56 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer