Roth S, Naber K, Scheer M, Gruenwaldt G, Lange H
Eur J Clin Pharmacol. 1976 Sep 30;10(5):357-65. doi: 10.1007/BF00565626.
Serum concentration, biological half-life, distribution space and serum clearance of sisomicin, a new aminoglycoside antibiotic, have been studied in twenty-three patients in comparison with the pharmacokinetics of 125I-labelled iothalamate, a compound only filtered by the kidney. 10 patients had normal or borderline abnormal serum creatinine (less than 1,5 mg/100 ml), 8 had various degrees of renal insufficiency (serum creatinine 1.7-9.6 mg/100 ml) and 6 were being treated by intermittent haemodialysis. After intravenous injection of sisomicin 1 mg/kg body weight in patients with normal or borderline renal function its half-life was 3.5 h, very similar to that of iothalamate, 3.2 h. The mean distribution space was 20.1% per cent of body weight; iothalamate, 23.7%. In patients with renal insufficiency there was a positive correlation between serum creatinine level and the half-life of sisomicin, and an even stronger correlation between the clearances of iothalamate and sisomicin. In patients dependent on haemodialysis, the mean serum half-life between dialysis was 40 h, compared to approximately 100 hours for iothalamate, which implies additional extrarenal clearance or tubular secretion of sisomicin. The results of pharmacokinetic studies indicated that a regime of sisomicin 1 mg/kg every 8 to 12 hours in patients with normal renal function would result in serum and urine levels sufficiently high to treat most urinary tract infections. In patients with impaired renal function the dosage interval should be increased according to the serum creatinine level, and in patients dependent on haemodialysis one standard dose at the end of each dialysis period should suffice. 9 patients with a chronic urinary tract infection severely complicated by an underlying disease were treated according to this dosage regimen with a satisfactory bacteriological and clinical result. No adverse reactions or signs of accumulation were observed.
已对23例患者研究了新氨基糖苷类抗生素西索米星的血清浓度、生物半衰期、分布容积和血清清除率，并与仅经肾脏滤过的化合物125I标记的碘他拉酸盐的药代动力学进行了比较。10例患者血清肌酐正常或临界异常（低于1.5mg/100ml），8例有不同程度的肾功能不全（血清肌酐1.7 - 9.6mg/100ml），6例正在接受间歇性血液透析治疗。在肾功能正常或临界肾功能的患者中静脉注射1mg/kg体重的西索米星后，其半衰期为3.5小时，与碘他拉酸盐的半衰期3.2小时非常相似。平均分布容积为体重的20.1%；碘他拉酸盐为23.7%。在肾功能不全的患者中，血清肌酐水平与西索米星的半衰期呈正相关，碘他拉酸盐和西索米星的清除率之间的相关性更强。在依赖血液透析的患者中，透析间期的平均血清半衰期为40小时，而碘他拉酸盐约为100小时，这意味着西索米星有额外的肾外清除或肾小管分泌。药代动力学研究结果表明，肾功能正常的患者每8至12小时给予1mg/kg西索米星的方案将使血清和尿液水平足够高，以治疗大多数尿路感染。肾功能受损的患者应根据血清肌酐水平增加给药间隔，而依赖血液透析的患者在每次透析结束时给予一个标准剂量就足够了。9例患有慢性尿路感染且因基础疾病而严重复杂化的患者按照该给药方案进行治疗，细菌学和临床结果均令人满意。未观察到不良反应或蓄积迹象。
