Rawlings J M, Hilton J, Trebilcock K L, Woollen B H, Wilks M F
Zeneca Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, England.
Fundam Appl Toxicol. 1994 Jul;23(1):93-100. doi: 10.1006/faat.1994.1084.
One important factor which may influence the extent and rate of percutaneous absorption is the dosing vehicle. The purpose of the experiments described was to compare the effect of dosing vehicles of different polarities on the absorption of two herbicides across rat skin in vivo. Rats were dosed dermally with either fluazifop-butyl (logP(oct) 4.5) or fomesafen sodium salt (logP(oct) -1.2) in propylene glycol (PG), octanol (OCT), or ethyl decanoate (ED), and the amount of radioactivity excreted in urine was determined. Absorption rates were estimated from the urinary excretion data and from blood kinetic data derived from intravenously dosed rats. For fluazifop-butyl the average rate of absorption (x10(-2) micrograms/hr-1 +/- SE) was not greatly influenced by the dosing vehicle (OCT, 2.94 +/- 0.08; ED, 3.66 +/- 0.10; PG, 3.95 +/- 0.32) despite relatively large differences in solubility (PG, 38 mg/ml; OCT, and ED, > 600 mg/ml). These results were consistent with the finding that there was at most only a twofold difference in the epidermal membrane:vehicle partition coefficients (km). In contrast, the absorption rate of fomesafen from PG (1.98 +/- 0.04) was approximately half that of ED (3.98 +/- 0.06) and OCT (4.49 +/- 0.08) for the first 30 hr after application and was in keeping with solubility data (PG, 638 mg/ml; OCT, 12 mg/ml; ED, < 10 mg/ml). At later time points the absorption of fomesafen from PG increased; this is discussed in relation to the penetration-enhancing properties of PG.(ABSTRACT TRUNCATED AT 250 WORDS)
可能影响经皮吸收程度和速率的一个重要因素是给药载体。所述实验的目的是比较不同极性的给药载体对两种除草剂在大鼠体内经皮肤吸收的影响。将大鼠经皮给予氟吡甲禾灵丁酯（辛醇/水分配系数logP(oct) 4.5）或乙羧氟草醚钠盐（logP(oct) -1.2），溶剂分别为丙二醇（PG）、辛醇（OCT）或癸酸乙酯（ED），并测定尿中排出的放射性物质的量。根据尿排泄数据以及静脉给药大鼠的血药动力学数据估算吸收速率。对于氟吡甲禾灵丁酯，尽管溶解度存在较大差异（PG为38 mg/ml；OCT和ED均>600 mg/ml），但给药载体对其平均吸收速率（×10(-2)微克/小时-1±标准误）影响不大（OCT为2.94±0.08；ED为3.66±0.10；PG为3.95±0.32）。这些结果与以下发现一致，即表皮膜与载体的分配系数（km）至多仅相差两倍。相比之下，在给药后的前30小时，乙羧氟草醚从PG的吸收速率（1.98±0.04）约为ED（3.98±0.06）和OCT（4.49±0.08）的一半，这与溶解度数据相符（PG为638 mg/ml；OCT为12 mg/ml；ED<10 mg/ml）。在之后的时间点，乙羧氟草醚从PG的吸收增加；这与PG的促渗透特性有关。（摘要截短至250字）
