Halstenson C E, Guay D R, Opsahl J A, Hirata C A, Olanoff L S, Novak E, Ko H, Cathcart K S, Matzke G R
Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis, Minnesota 55415.
Antimicrob Agents Chemother. 1990 Apr;34(4):519-23. doi: 10.1128/AAC.34.4.519.
The disposition of cefmetazole was studied in 25 subjects with various degrees of renal function after a 1,000-mg, constant-rate, 30-min intravenous infusion of cefmetazole sodium. In six subjects with creatinine clearance (CLCR) of greater than 90 ml/min per 1.73 m2 (group 1), the terminal elimination half-life (t1/2 beta) was 1.31 +/- 0.54 h (mean +/- standard deviation), cefmetazole total body clearance (CLP) was 132.8 +/- 25.1 ml/min per 1.73 m2, and volume of distribution at steady state was 0.165 +/- 0.025 liter/kg. The fraction of dose excreted unchanged in the urine was 84.0% +/- 26.1%. Subjects with CLCRS of 40 to 69 (group 2, n = 6) and 10 to 39 (group 3, n = 6) ml/min per 1.73 m2 demonstrated prolongation of the t1/2 beta (3.62 +/- 1.06 and 5.93 +/- 1.81 h, respectively) and significant reductions in cefmetazole CLP (52.8 +/- 14.3 and 30.2 +/- 10.2 ml/min per 1.73 m2, respectively), compared with group 1. In seven subjects on chronic hemodialysis (group 4) studied during an interdialytic period, the cefmetazole t1/2 beta was increased to 24.10 +/- 8.12 h and the CLP was reduced to 6.8 +/- 2.1 ml/min per 1.73 m2. Cefmetazole CLP correlated positively with CLCR (r = 0.951, P less than 0.001): CLP = (1.181 . CLCR) -- 0.287. The disposition of cefmetazole was also assessed in six group 4 subjects during an intradialytic period. The t1/2 beta during hemodialysis (2.09 +/- 0.69 h) was significantly shorter than that observed during the interdialytic period. The hemodialysis clearance of cefmetazole was 86.1 +/- 20.1 ml/min, and the fraction of cefmetazole removed during hemodialysis was 59.8% +/- 5.9%. It is recommended that patients with renal insufficiency received standard doses of cefmetazole at extended intervals and patients on maintenance hemodialysis received standard doses after hemodialysis.
在25名肾功能程度各异的受试者中，静脉恒速输注1000毫克头孢美唑钠30分钟后，对头孢美唑的处置情况进行了研究。在6名肌酐清除率（CLCR）大于90毫升/分钟/1.73平方米的受试者（第1组）中，终末消除半衰期（t1/2β）为1.31±0.54小时（平均值±标准差），头孢美唑的全身清除率（CLP）为132.8±25.1毫升/分钟/1.73平方米，稳态分布容积为0.165±0.025升/千克。尿中以原形排泄的剂量分数为84.0%±26.1%。CLCR为40至69（第2组，n = 6）和10至39（第3组，n = 6）毫升/分钟/1.73平方米的受试者，与第1组相比，t1/2β延长（分别为3.62±1.06和5.93±1.81小时），头孢美唑CLP显著降低（分别为52.8±14.3和30.2±10.2毫升/分钟/1.73平方米）。在7名慢性血液透析患者（第4组）透析间期进行研究时，头孢美唑的t1/2β增至24.10±8.12小时，CLP降至6.8±2.1毫升/分钟/1.73平方米。头孢美唑CLP与CLCR呈正相关（r = 0.951，P＜0.001）：CLP =（1.181×CLCR）-0.287。还在第4组的6名受试者透析期评估了头孢美唑的处置情况。血液透析期间的t1/2β（2.09±0.69小时）显著短于透析间期观察到的t1/2β。头孢美唑的血液透析清除率为86.1±20.1毫升/分钟，血液透析期间清除的头孢美唑分数为59.8%±5.9%。建议肾功能不全患者延长给药间隔给予标准剂量的头孢美唑，维持性血液透析患者在透析后给予标准剂量。
