Leroy A, Fillastre J P, Borsa-Lebas F, Etienne I, Humbert G
Department of Biochemistry, University of Rouen, Hôpital Charles Nicolle, France.
Antimicrob Agents Chemother. 1992 Dec;36(12):2794-8. doi: 10.1128/AAC.36.12.2794.
The pharmacokinetics of meropenem (ICI 194,660) and its open-ring metabolite (ICI 213,689) were studied in 6 healthy volunteers and 16 patients with moderate to severe renal impairment after a single intravenous dose of 500 mg given as a 30-min infusion. Concentrations of unchanged meropenem in plasma and urine were measured by both microbiological and high-pressure liquid chromatographic (HPLC) assays. A good correlation was found between the two techniques. Pharmacokinetic parameters of unchanged meropenem were determined by using the HPLC data. The terminal half-life of unchanged meropenem increased in relation to the degree of renal impairment, being 1.2 h in subjects with normal renal function and 10 h in patients with end-stage renal failure. Total body clearance and renal clearance of unchanged meropenem are linearly related to creatinine clearance. The concentrations of the metabolite in plasma, which are very low in healthy subjects, significantly increased in uremic patients. The apparent half-life of ICI 213,689 increased in uremic patients and was about 35 h in patients with severe renal insufficiency. Meropenem and its metabolite are effectively removed by hemodialysis. The dialysis clearance of the unchanged drug was 81 +/- 22 ml/min. Dosage adjustments of meropenem will be necessary in patients with severe renal impairment.
对6名健康志愿者和16名中重度肾功能不全患者在单次静脉输注500mg美罗培南（ICI 194,660）30分钟后，研究了其药代动力学及开环代谢产物（ICI 213,689）的药代动力学。采用微生物学和高压液相色谱（HPLC）法测定血浆和尿液中未改变的美罗培南浓度。发现这两种技术之间具有良好的相关性。利用HPLC数据确定未改变的美罗培南的药代动力学参数。未改变的美罗培南的终末半衰期随肾功能损害程度增加，肾功能正常受试者为1.2小时，终末期肾衰竭患者为10小时。未改变的美罗培南的总体清除率和肾清除率与肌酐清除率呈线性相关。代谢产物在血浆中的浓度在健康受试者中很低，在尿毒症患者中显著升高。ICI 213,689的表观半衰期在尿毒症患者中增加，在严重肾功能不全患者中约为35小时。美罗培南及其代谢产物可通过血液透析有效清除。未改变药物的透析清除率为81±22ml/min。严重肾功能不全患者需要调整美罗培南的剂量。
