Hosie K, Gilbert J A, Kerr D, Brown C B, Peers E M
Northern General Hospital, Sheffield, United Kingdom.
Drug Deliv. 2001 Jan-Mar;8(1):9-12. doi: 10.1080/107175401300002694.
Interest in targeting drugs into the peritoneal cavity for intra-abdominal cancers or infections is undergoing a revival as recent clinical trials have demonstrated, not only a regional advantage in concentration of the active agent, but also improved long-term outcomes. Solutions currently used for intraperitoneal (IP) drug delivery have short residence times, however, which can limit the exposure of all areas of the peritoneum to the active agent. Icodextrin 4% solution was compared with saline and a glucose-based peritoneal dialysis solution in a clinical study of IP residence time. The study was carried out during the fortnightly rest phase in 9 patients undergoing 5-fluorouracil (5-Fu) IP treatment for colorectal cancer. The volume remaining in the peritoneal cavity was measured at 0, 12, 24, 48, 72, and 96 hr after an instillation of 2 liters of each fluid. Saline (n = 3 dwells) and glucose (n = 3 dwells) peritoneal dialysis solutions were almost fully absorbed by 24 hr, and the patients experienced discomfort when using these solutions. In contrast, icodextrin 4% solution (n = 188 dwells) maintained its instilled volume for up to 48 hr, and half the instilled volume remained after 72 and 96 hr. This result would allow extensive and prolonged coverage of the peritoneal surface. Icodextrin 4% solution may be an effective vehicle to deliver therapeutic agents into the peritoneal cavity.
将药物靶向输送至腹腔以治疗腹内癌症或感染正重新受到关注，正如近期临床试验所表明的，这不仅在活性剂浓度方面具有区域优势，而且能改善长期疗效。然而，目前用于腹腔内（IP）给药的溶液停留时间较短，这可能会限制腹膜所有区域与活性剂的接触。在一项关于IP停留时间的临床研究中，对4%艾考糊精溶液与生理盐水和一种基于葡萄糖的腹膜透析溶液进行了比较。该研究在9例接受5-氟尿嘧啶（5-Fu）腹腔内治疗结直肠癌的患者每两周一次的休息期进行。在分别注入2升每种液体后的0、12、24、四十八、七十二和九十六小时测量腹腔内剩余的液体量。生理盐水（n = 3次灌注）和葡萄糖（n = 3次灌注）腹膜透析溶液在24小时时几乎被完全吸收，并且患者在使用这些溶液时感到不适。相比之下，4%艾考糊精溶液（n = 188次灌注）可将注入的液体量维持长达48小时，在72和96小时后仍有一半注入量留存。这一结果将使腹膜表面得到广泛且持久的覆盖。4%艾考糊精溶液可能是一种将治疗剂输送至腹腔的有效载体。
