Goodman E L, Van Gelder J, Holmes R, Hull A R, Sanford J P
Antimicrob Agents Chemother. 1975 Oct;8(4):434-8. doi: 10.1128/AAC.8.4.434.
In patients with impaired renal function, careful adjustment of gentamicin dosage is required to achieve therapeutic yet nontoxic concentrations. Two regimens that differ in pharmacodynamic characteristics have been recommended for this purpose: prolonging the intervals between administration of equal doses (variable frequency regimen [VFR]) or administering a loading dose followed at the usual intervals by reduced maintenance doses (variable dosage regimen [VDR]). These regimens were compared in a prospective, randomized study of 20 seriously ill hospitalized patients, 10 on VFR and 10 on VDR. Wide variability in peak serum levels of gentamicin was observed both between patients and in individual patients after separate injections of the same dosage. As predicted by the design of these regimens, the trough serum levels of gentamicin correlated significantly with the serum creatinine concentrations in patients on the VDR but not in patients on the VFR. A gentamicin trough level of >/=4 mug/ml was the only variable among those tested that correlated significantly with development or progression of renal insufficiency during treatment with gentamicin, but such trough levels were observed frequently on both regimens. Whereas this study does not permit a direct comparison of the therapeutic efficacy of VDR and VFR, no difference in the risk of nephrotoxicity with these regimens was observed.
对于肾功能受损的患者，需要仔细调整庆大霉素剂量，以达到治疗浓度且无毒副作用。为此推荐了两种药效学特征不同的给药方案：延长等剂量给药的间隔时间（可变频率方案[VFR]）或先给予负荷剂量，随后按常规间隔给予减量维持剂量（可变剂量方案[VDR]）。在一项针对20例重症住院患者的前瞻性随机研究中对这两种方案进行了比较，其中10例采用VFR，10例采用VDR。在患者之间以及同一患者单独注射相同剂量后，庆大霉素的血清峰值水平存在很大差异。正如这些方案的设计所预测的那样，VDR患者的庆大霉素谷值水平与血清肌酐浓度显著相关，而VFR患者则不然。庆大霉素谷值水平≥4μg/ml是所检测的变量中唯一与庆大霉素治疗期间肾功能不全的发生或进展显著相关的变量，但两种方案中均频繁观察到这样的谷值水平。虽然这项研究不允许直接比较VDR和VFR的治疗效果，但未观察到这两种方案在肾毒性风险方面存在差异。
