Watanabe Y, van Hoogdalem E J, de Boer A G, Breimer D D
Bio-Pharmaceutical Sciences, Sylvius Labs, Leiden University, The Netherlands.
J Pharm Sci. 1988 Oct;77(10):847-9. doi: 10.1002/jps.2600771007.
The enhancing effect of the medium chain monoglycerides glyceryl-1-monoctanoate (GMO), glyceryl-1-monodecanoate (GMD), and glyceryl-1-monododecanoate (GMDD) on rectal absorption of the cephalosporin antibiotic cefoxitin [(6R,7S)-3-hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5- thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid carbamate (ester)] was investigated in unanesthetized rats. Rectal infusion of 3 mg of cefoxitin sodium without monoglyceride resulted in a mean bioavailability of 31 +/- 18% and a mean residence time (MRT) of 134 +/- 44 min. Coadministration with 53% (w/w) GMO significantly enhanced cefoxitin absorption, resulting in a mean bioavailability of 84 +/- 11% and a mean MRT of 75 +/- 8 min. In a lower concentration, GMD (13% w/w) also significantly promoted cefoxitin bioavailability to 68 +/- 14% and reduced MRT to 70 +/- 11 min. With GMDD only, a trend of increasing bioavailability with increasing monoglyceride concentration was observed, which may be explained by its limited aqueous solubility. Concerning the action of GMO and GMD, the longer monoglyceride is, in terms of effective concentration, more potent in enhancing the extent and rate of cefoxitin absorption. However, a further increase in chain length results in a loss of effect, indicating that the effect of monoglycerides on drug absorption may be determined by their intrinsic absorption enhancing action and solubility.
在未麻醉的大鼠中研究了中链单甘油酯1-单辛酸甘油酯（GMO）、1-单癸酸甘油酯（GMD）和1-单月桂酸甘油酯（GMDD）对头孢菌素抗生素头孢西丁[（6R，7S）-3-羟甲基）-7-甲氧基-8-氧代-7-[2-（2-噻吩基）乙酰胺基]-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸氨基甲酸酯（酯）]直肠吸收的增强作用。直肠输注3mg不含单甘油酯的头孢西丁钠，平均生物利用度为31±18%，平均驻留时间（MRT）为134±44分钟。与53%（w/w）的GMO共同给药显著增强了头孢西丁的吸收，平均生物利用度为84±11%，平均MRT为75±8分钟。在较低浓度下，GMD（13%w/w）也显著促进了头孢西丁的生物利用度至68±14%，并将MRT降低至70±11分钟。仅使用GMDD时，观察到随着单甘油酯浓度增加生物利用度增加的趋势，这可能是由于其有限的水溶性所致。关于GMO和GMD的作用，就有效浓度而言，单甘油酯链越长，增强头孢西丁吸收程度和速率的效力越强。然而，链长的进一步增加导致效果丧失，表明单甘油酯对药物吸收的作用可能由其内在的吸收增强作用和溶解度决定。
