Watanabe M, Saito I, Mitsuhashi S, Koyama M, Kawaguchi Y
Jpn J Antibiot. 1985 Apr;38(4):1086-92.
Following the previous report on pharmacokinetics of micronomicin (MCR) in healthy volunteers, pharmacokinetic studies were made again in patients with different degree of renal impairment, and a nomogram was obtained. MCR at a dose of 60 mg/time was given by 1-hour drip infusion to 14 inpatients who consented to receive MCR (age: 35 to 84 years, Ccr: 17.96 to 104.35 ml/min). The blood collection was performed in accordance with the schedule made upon the degree of renal impairment, and the serum concentration was determined by HPLC method. The results were analyzed by MULT program using two- or one-compartment open model. The serum concentration (Cmax) just after administration of MCR was 5.8 +/- 0.9 microgram/ml (mean +/- S.D.). The biological half-life was 1.81 to 12.35 hours. Taking the above results into consideration together with the previous ones of healthy males, the following correlation was obtained between the elimination constant (Kel or beta) and Ccr calculated from S-Cr.: Kel or beta = 0.0038 X Ccr - 0.0097. Further, no side effect was observed in these studies. Elimination of MCR from blood was dependent on renal function like other aminoglycosides, and so it was possible to estimate the elimination constant from Ccr. From these results, a nomogram for the optimum dosage regimen of MCR was obtained.
继之前关于小诺米星（MCR）在健康志愿者体内药代动力学的报告之后，又对不同程度肾功能损害的患者进行了药代动力学研究，并得出了一张列线图。对14名同意接受MCR的住院患者（年龄：35至84岁，内生肌酐清除率：17.96至104.35 ml/min），以60 mg/次的剂量进行1小时静脉滴注给予MCR。根据肾功能损害程度制定的时间表进行采血，并采用高效液相色谱法测定血清浓度。结果用MULT程序以二室或一室开放模型进行分析。MCR给药后即刻的血清浓度（Cmax）为5.8±0.9微克/毫升（平均值±标准差）。生物半衰期为1.81至12.35小时。将上述结果与之前健康男性的结果综合考虑，得出消除常数（Kel或β）与根据血清肌酐计算出的内生肌酐清除率之间的以下相关性：Kel或β = 0.0038×内生肌酐清除率 - 0.0097。此外，在这些研究中未观察到副作用。与其他氨基糖苷类药物一样，MCR从血液中的消除依赖于肾功能，因此可以根据内生肌酐清除率估算消除常数。根据这些结果，得出了MCR最佳给药方案的列线图。
