Roivas L, Kivistö K T, Neuvonen P J
Department of Pharmacology, University of Turku, Finland.
Int J Clin Pharmacol Ther. 1994 Jul;32(7):365-9.
The gastrointestinal absorption of furosemide preadsorbed onto activated charcoal was studied in 8 healthy volunteers using a randomized cross-over design with 3 phases. The 3 experimental furosemide formulations were capsules containing 40 mg furosemide only (reference) or 100 mg furosemide preadsorbed onto 160 mg or 200 mg charcoal. Timed plasma samples were taken and urine was collected for 24 hours for determination of drug concentrations and diuretic response. The release of furosemide from the formulations was also studied in vitro. Furosemide was found to dissolve rapidly from the reference formulation, whereas it was slowly desorbed from charcoal with the cumulative release reaching 50-60% in 24 hours (pH 5.3). The absorption rate of furosemide was smaller after intake of the charcoal formulations that after intake of the reference formulation. However, also the amounts of furosemide found in plasma and urine were clearly decreased due to preadsorption onto charcoal. The dose-adjusted relative bioavailabilities of the furosemide-charcoal formulations (compared to the reference formulation) remained less than 10%. The release mechanism of furosemide from charcoal is sensitive to physiological factors of the gastrointestinal tract. The large variability known to be typical for furosemide absorption was further increased when the drug was preadsorbed onto charcoal.
采用随机交叉设计的三个阶段，在8名健康志愿者中研究了预吸附在活性炭上的速尿的胃肠道吸收情况。三种实验性速尿制剂为仅含40毫克速尿的胶囊（参比制剂）或预吸附在160毫克或200毫克活性炭上的100毫克速尿。定时采集血样并收集24小时尿液，以测定药物浓度和利尿反应。还对速尿从制剂中的释放情况进行了体外研究。发现速尿从参比制剂中迅速溶解，而其从活性炭上缓慢解吸，在24小时内（pH 5.3）累积释放率达到50 - 60%。服用含活性炭制剂后速尿的吸收速率小于服用参比制剂后的吸收速率。然而，由于预吸附在活性炭上，血浆和尿液中速尿的含量也明显降低。速尿 - 活性炭制剂的剂量校正相对生物利用度（与参比制剂相比）仍低于10%。速尿从活性炭上的释放机制对胃肠道的生理因素敏感。当药物预吸附在活性炭上时，已知速尿吸收典型的较大变异性进一步增加。
