Ahmad Maqsood, Ghumman Shazia Akram, Sher Alamgeer, Sharif Tanveer, Sher Muhammad, Abbas Tahir
College of Pharmacy GC University Faisalabad.
Department of Pharmacy University of Sargodha, Sargodha, Pakistan.
Iran J Pharm Res. 2012 Winter;11(1):69-75.
Several modalities of drug administration have been investigated to improve bioavailability and to reduce 5-FU related toxicity. The aim of present study was to evaluate the effect of skimmed milk on the absorption and metabolism of 5-FU in rabbits, mice and dogs. It was further aimed to determine its route related toxicity in rabbits. Plasma concentration of both 5-FU and its metabolite 5-Fluoro-2-deoxyuridine (5-Fdurd) was determined using HPLC. The absorption of 5-FU co-administered with skimmed milk was significantly higher as compared to its co-administration with water in rabbits and mice (p < 0.001), whereas no significant difference was observed in dogs. The plasma concentration of 5-Fdurd a major metabolite of 5-FU was significantly higher in water group when compared with skimmed milk group in rabbits and mice (p < 0.05), whereas no significant difference was observed in dogs. Route related toxicity was also determined in rabbits. Various hematological parameters were studied at 4(th) and 7(th) day after oral and intravenous administration of 5-FU. WBCs count was significantly decreased in intravenous group as compared to control and oral groups (p < 0.001). It was concluded that co-administration of skimmed milk with 5-FU increases its absorption and reduces its metabolism. Skimmed milk also reduces 5-FU related toxicity in rabbits.
为了提高生物利用度并降低与5-氟尿嘧啶（5-FU）相关的毒性，人们对几种给药方式进行了研究。本研究的目的是评估脱脂牛奶对兔、小鼠和犬体内5-FU吸收和代谢的影响。进一步确定其在兔体内的给药途径相关毒性。使用高效液相色谱法（HPLC）测定5-FU及其代谢产物5-氟-2-脱氧尿苷（5-Fdurd）的血浆浓度。与在兔和小鼠中5-FU与水共同给药相比，5-FU与脱脂牛奶共同给药时的吸收显著更高（p<0.001），而在犬中未观察到显著差异。在兔和小鼠中，与脱脂牛奶组相比，5-FU的主要代谢产物5-Fdurd的血浆浓度在水组中显著更高（p<0.05），而在犬中未观察到显著差异。还在兔中确定了给药途径相关毒性。在口服和静脉注射5-FU后的第4天和第7天研究了各种血液学参数。与对照组和口服组相比，静脉注射组的白细胞计数显著降低（p<0.001）。得出的结论是，5-FU与脱脂牛奶共同给药可增加其吸收并减少其代谢。脱脂牛奶还可降低兔体内与5-FU相关的毒性。
