Conte J E
Department of Epidemiology and Biostatistics, University of California, San Francisco 94143-0208.
J Clin Pharmacol. 1994 Nov;34(11):1066-70. doi: 10.1002/j.1552-4604.1994.tb01982.x.
The pharmacokinetics of single, 1- or 2-g intravenous doses of cefodizime were studied in subjects with normal, impaired renal function or requiring chronic hemodialysis. Drug concentrations were measured using high-performance liquid chromatography. Forty-five subjects (20 with creatinine clearance of > or = 90 mL/min, 15 with creatine clearances between 5 and 89 mL/min, and 10 requiring chronic hemodialysis) were studied. The concentration-time curve of cefodizime was best represented by an open two-compartment model. The elimination half-lives in subjects with normal (Group 1) and impaired renal function (Group 2) or requiring chronic hemodialysis (Group 3) were 4.14 +/- 1.55, 5.10 +/- 2.24, and 10.1 +/- 6.01 hours, respectively (Group 3 versus 1 or 2, P < .05; Group 1 versus 2, P > .05). The total body (serum) clearances in the same groups were 3 +/- 0.52, 2.22 +/- 0.61, and 0.99 +/- 0.33 L/hour, respectively (Group 1 versus 2 or 3, P < .05; Group 2 versus 3, P < .05). Although renal function has an effect on the pharmacokinetics of cefodizime, its effect on the elimination half life is marginal in subjects with creatinine clearance of more than 25 mL/min. In individuals with more severe renal impairment or those requiring chronic hemodialysis, dosage adjustment would be required.
在肾功能正常、受损或需要长期血液透析的受试者中，研究了单次静脉注射1克或2克头孢地嗪的药代动力学。使用高效液相色谱法测量药物浓度。共研究了45名受试者（20名肌酐清除率≥90毫升/分钟，15名肌酐清除率在5至89毫升/分钟之间，10名需要长期血液透析）。头孢地嗪的浓度-时间曲线最适合用开放二室模型表示。肾功能正常组（第1组）、肾功能受损组（第2组）或需要长期血液透析组（第3组）的消除半衰期分别为4.14±1.55、5.10±2.24和10.1±6.01小时（第3组与第1组或第2组相比，P<.05；第1组与第2组相比，P>.05）。相同组别的全身（血清）清除率分别为3±0.52、2.22±0.61和0.99±0.33升/小时（第1组与第2组或第3组相比，P<.05；第2组与第3组相比，P<.05）。虽然肾功能对头孢地嗪的药代动力学有影响，但在肌酐清除率超过25毫升/分钟的受试者中，其对消除半衰期的影响很小。对于肾功能损害更严重的个体或需要长期血液透析的个体，需要调整剂量。
