Strait Karen R, Orkin Jack L, Anderson Daniel C, Muly E Chris
Division of Animal Resources, Yerkes National Primate Research Center, Atlanta, GA, USA.
J Am Assoc Lab Anim Sci. 2010 Mar;49(2):207-14.
As part of a study of antipsychotic drug treatment in monkeys, we developed a technique to provide chronic, constant-rate, gastric drug infusion in nontethered rhesus macaques. This method allowed us to mimic the osmotic release oral delivery system currently used in humans for continuous enteral drug delivery. Rhesus macaques (n = 5) underwent gastric catheter placement by laparotomy. After the catheters were secured to the stomach, the remaining catheter length was exited through the lateral abdomen, tunneled subcutaneously along the back, and connected to a 2-mL osmotic pump enclosed in a subcutaneous pocket. Osmotic pumps were changed every 2 to 4 wk for 1 y and remained patent for the duration of the study. Four complications (including cutting of the catheter, incisional dehiscence at the pump site, and loss of 1 catheter into the abdominal cavity requiring catheter replacement) occurred among the 80 pump changes performed during the year-long study. At necropsy, histopathologic examination of the catheter implant sites revealed mild changes consistent with a foreign-body reaction. Our results indicate that the gastric catheter and osmotic pump system was well tolerated in rhesus macaques for as long as 12 mo after placement and suggest that this system will be an attractive option for use in studies that require chronic, constant-rate, gastric drug infusion in nontethered monkeys.
作为对猴子进行抗精神病药物治疗研究的一部分,我们开发了一种技术,用于在未系绳的恒河猴中进行慢性、恒速胃内药物输注。这种方法使我们能够模拟目前人类用于持续肠内给药的渗透释放口服给药系统。对5只恒河猴进行剖腹术放置胃导管。将导管固定在胃上后,剩余的导管长度从侧腹穿出,沿背部皮下潜行,并连接到置于皮下袋中的一个2毫升渗透泵。在1年的时间里,每2至4周更换一次渗透泵,在研究期间导管一直保持通畅。在为期一年的研究中进行的80次泵更换过程中,出现了4例并发症(包括导管切断、泵部位切口裂开以及1根导管掉入腹腔需要更换导管)。尸检时,对导管植入部位的组织病理学检查显示有与异物反应一致的轻微变化。我们的结果表明,胃导管和渗透泵系统在恒河猴体内放置后长达12个月的时间里耐受性良好,这表明该系统将是在需要对未系绳猴子进行慢性、恒速胃内药物输注的研究中一个有吸引力的选择。