Barr W H, Colucci R, Radwanski E, Zampaglione N, Cutler D, Lin C C, Elliott M, Affrime M B
Department of Pharmacy and Pharmaceutics, Virginia Commonwealth University, Richmond 23298-0533, USA.
J Chemother. 1995 Jun;7 Suppl 2:53-61.
Isepamicin is a new aminoglycoside that has activity against many bacteria resistant to other aminoglycosides. The pharmacokinetics of isepamicin have been characterized in neonatal, pediatric, adult, elderly and renally impaired human populations as well as in clinical trials using the techniques of population pharmacokinetics. The pharmacokinetics of isepamicin are uncomplicated and generally similar to those of other aminoglycosides, although there is some evidence that it may have less tissue accumulation. The drug is completely absorbed following intramuscular administration. The drug is not metabolized and unchanged isepamicin accounts for all of the drug substance in plasma and urine. It is completely eliminated via the renal route; consequently dosing in patients with renal insufficiency has to be adjusted according to the degree of renal impairment. The pharmacokinetics of isepamicin are generally linear. Thus peak plasma concentrations and area under the plasma concentration curve (AUC) values are proportional to the administered dose while clearance (1.1-1.3 mL/min/kg), volume of distribution at steady state (0.23-0.29 L/kg) and half-life (2-2.5 h) are independent of dose. There is no significant accumulation of drug in the plasma with once- or twice-daily dosing. The isepamicin plasma concentration curve following a 1 g intravenous dose to healthy volunteers can be best characterized by a tri-exponential curve corresponding to a t1/2 alpha of 0.17 h, a t1/2 beta of 2.1 h, and a gamma-phase of 34 h. The t1/2 beta represents the elimination phase and changes with age and renal functions, while the gamma-phase represents the return of drug to plasma from a deep compartment including binding in renal tissue. The gamma-phase represents less than 3% of the total AUC and does not change with age. Isepamicin readily distributes to extracellular fluid and pulmonary tissue. In conclusion, isepamicin demonstrates predictable linear kinetics and is similar pharmacokinetically to other aminoglycosides. Preliminary indications of decreased tissue accumulation implied from pharmacokinetic and pharmacodynamic characteristics of isepamicin favour once-daily dosing.
异帕米星是一种新型氨基糖苷类抗生素，对许多耐其他氨基糖苷类抗生素的细菌具有活性。异帕米星的药代动力学已在新生儿、儿童、成人、老年人和肾功能受损人群中以及在采用群体药代动力学技术的临床试验中得到了表征。异帕米星的药代动力学并不复杂，总体上与其他氨基糖苷类抗生素相似，不过有一些证据表明它的组织蓄积可能较少。该药物肌内注射后可完全吸收。药物不被代谢，血浆和尿液中的药物成分均为未变化的异帕米星。它通过肾脏途径完全消除；因此，肾功能不全患者的给药剂量必须根据肾功能损害程度进行调整。异帕米星的药代动力学通常呈线性。因此，血浆峰浓度和血浆浓度曲线下面积（AUC）值与给药剂量成正比，而清除率（1.1 - 1.3 mL/min/kg）、稳态分布容积（0.23 - 0.29 L/kg）和半衰期（2 - 2.5小时）与剂量无关。每日一次或两次给药时，血浆中无明显药物蓄积。对健康志愿者静脉注射1 g剂量后，异帕米星的血浆浓度曲线可用三指数曲线最佳表征，其α半衰期为0.17小时，β半衰期为2.1小时，γ相为34小时。β半衰期代表消除相，随年龄和肾功能而变化，而γ相代表药物从包括肾脏组织结合在内的深部隔室返回血浆。γ相占总AUC的比例不到3%，且不随年龄变化。异帕米星易于分布到细胞外液和肺组织。总之，异帕米星表现出可预测的线性动力学，药代动力学上与其他氨基糖苷类抗生素相似。异帕米星药代动力学和药效学特征所暗示的组织蓄积减少的初步迹象支持每日一次给药。
