Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasaginakauchi-cho 5, Yamashina-ku, Kyoto 6078414, Japan.
Eur J Pharm Sci. 2011 Oct 9;44(3):410-5. doi: 10.1016/j.ejps.2011.08.024. Epub 2011 Sep 1.
The variety of physiologic and biologic functions of zinc is expected to enable the development of zinc-related medicines. In this study, the distribution of endogenous zinc, the disposition after intravenous injection, and the intestinal absorption of zinc were investigated in vivo using rats from the viewpoints of pharmaceutical science and pharmacokinetics. High levels of endogenous zinc were observed in bone, testis, and liver. RT-PCR analysis on the mRNA of metallothionein in tissues clarified that it is significantly correlated with the distribution of zinc, suggesting that zinc is accumulated in tissues as a complex with MT. Following intravenous injection, uptake of zinc was high in liver, spleen, pancreas, kidney, and intestine. Fractional absorptions of zinc after oral administration to fasted rats were greater than those to fed rats, suggesting that some factors in diet inhibit the absorption of zinc. In fasted rats, fractional absorption was slightly decreased in high-dose group, suggesting the involvement of carrier-mediated transport. Study utilizing an in situ closed-loop method also indicated saturable intestinal absorption of zinc. These findings will further the research and development of zinc-related medicines by providing basic and important information on zinc.
锌的多种生理和生物学功能有望使锌相关药物得以发展。本研究从药物科学和药代动力学的角度,利用大鼠体内实验,研究了内源性锌的分布、静脉注射后的处置以及锌的肠道吸收。骨、睾丸和肝脏中观察到高水平的内源性锌。组织中金属硫蛋白 mRNA 的 RT-PCR 分析表明,它与锌的分布显著相关,提示锌作为 MT 的复合物在组织中积累。静脉注射后,锌在肝脏、脾脏、胰腺、肾脏和肠道中的摄取量很高。给予禁食大鼠口服锌后,其分数吸收大于给予进食大鼠,提示饮食中的某些因素抑制了锌的吸收。在禁食大鼠中,高剂量组的分数吸收略有下降,提示载体介导的转运参与其中。利用原位闭路循环法进行的研究也表明锌的肠道吸收呈饱和状态。这些发现将为锌相关药物的研究和开发提供基础和重要信息,从而进一步推进这方面的工作。