Turkall R M, Skowronski G A, Kadry A M, Abdel-Rahman M S
Pharmacology and Toxicology Department, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark 07103-2714.
Arch Environ Contam Toxicol. 1994 May;26(4):504-9. doi: 10.1007/BF00214154.
The aim of this study was to utilize pharmacokinetic techniques to assess the bioavailability of sandy or clay soil-adsorbed naphthalene vs chemical alone following dermal treatment of male rats. Animals were exposed to 43 micrograms total of 14C-naphthalene (pure or adsorbed to one of two soils) introduced into a shallow glass cap covering a 13-cm2 area on the skin of each rat. While both soils delayed the time to reach maximum plasma concentration of radioactivity and significantly increased the half-life of plasma absorption, only sandy soil significantly decreased the peak plasma concentration of radioactivity versus the pure compound. Within 12 h after dermal application, approximately 50% of the naphthalene dose was excreted in the urine of the pure and clay soil-adsorbed groups. However, when naphthalene was adsorbed to sandy soil, the percentages of the initial dose excreted in the urine collected between 0-12 h and 12-24 h were nearly equal (33-39%). Furthermore, sandy soil adsorption shifted the secondary excretion route from expired air to feces and significantly lowered the amount of radioactivity in expired air relative to naphthalene alone. In the presence of sandy soil, a significantly larger amount of radioactivity washed off of the skin application sites. In all groups the predominant urinary metabolites determined by high performance liquid chromatography were 2,7- and 1,2-dihydroxynaphthalenes.
本研究的目的是运用药代动力学技术,评估雄性大鼠经皮肤处理后,沙质或黏质土壤吸附萘与单独化学药剂相比的生物利用度。将总共43微克的14C-萘(纯品或吸附于两种土壤之一)导入覆盖每只大鼠13平方厘米皮肤区域的浅玻璃罩中,使动物接触。虽然两种土壤都延迟了达到放射性血浆浓度最大值的时间,并显著增加了血浆吸收的半衰期,但只有沙质土壤与纯化合物相比显著降低了放射性血浆浓度峰值。经皮肤给药后12小时内,纯品组和黏质土壤吸附组中约50%的萘剂量经尿液排出。然而,当萘吸附于沙质土壤时,在0 - 12小时和12 - 24小时收集的尿液中排出的初始剂量百分比几乎相等(33 - 39%)。此外,沙质土壤吸附使次要排泄途径从呼出空气转变为粪便,并相对于单独的萘显著降低了呼出空气中的放射性量。在有沙质土壤存在的情况下,从皮肤涂抹部位洗去的放射性量显著更大。在所有组中,通过高效液相色谱法测定的主要尿液代谢物为2,7 - 二羟基萘和1,2 - 二羟基萘。