Martyn J A, Greenblatt D J, Abernethy D R
JAMA. 1985 Mar 1;253(9):1288-91.
To determine the etiology of the decreased efficacy of cimetidine in burned and critically ill surgical patients, we studied the kinetics and dynamics of the drug in eight burned patients at a mean of 12 days after the burn. The kinetics were compared with those of nine healthy controls. The elimination half-life of cimetidine in burned patients was significantly reduced (2.2 v 1.5 hours), and total clearance significantly increased (8.2 v 13.3 mL/min/kg). Creatinine and total cimetidine clearance were highly correlated with size of the burn. In the patients studied, 63% of the dose was excreted in eight hours, compared with 45% after 24 hours in controls. Gastric pH was maintained at 4 or higher as long as plasma levels of cimetidine were held above 0.5 microgram/mL. Thus, the increased clearance of cimetidine might explain the decreased effectiveness of this drug in burned and possibly other surgical patients. Dose schedules may need to be altered to compensate for the enhanced clearance of this drug.
为确定西咪替丁在烧伤及重症外科患者中疗效降低的病因,我们研究了8例烧伤患者在烧伤后平均12天使用该药的动力学和药效学情况。将其动力学情况与9名健康对照者进行了比较。烧伤患者中西咪替丁的消除半衰期显著缩短(2.2对1.5小时),总清除率显著升高(8.2对13.3毫升/分钟/千克)。肌酐清除率和西咪替丁总清除率与烧伤面积高度相关。在所研究的患者中,63%的剂量在8小时内排出,而对照者在24小时后排出45%。只要西咪替丁血浆水平维持在0.5微克/毫升以上,胃内pH值就能维持在4或更高。因此,西咪替丁清除率增加可能解释了该药在烧伤患者以及可能在其他外科患者中疗效降低的原因。可能需要调整给药方案以补偿该药清除率的提高。