Halstenson C E, Opsahl J A, Schwenk M H, Kovarik J M, Puri S K, Ho I, Matzke G R
Department of Medicine, Hennepin County Medical Center, Minneapolis, Minnesota.
Antimicrob Agents Chemother. 1990 Mar;34(3):385-9. doi: 10.1128/AAC.34.3.385.
The disposition of roxithromycin, an investigational macrolide antibiotic, was evaluated in 20 subjects, 10 with normal renal function (creatinine clearance [CLCR] of 116 +/- 17 ml/min [mean +/- standard deviation]) and 10 with severely impaired renal function (CLCR of 10.2 +/- 2.6 ml/min) after a single 300-mg oral dose. Plasma concentration-time data were analyzed in terms of a one- or two-compartment oral absorption model utilizing nonlinear regression analysis. The terminal elimination half-life was significantly prolonged in the group with severely impaired renal function (15.5 +/- 4.7 h) compared with that of the group with normal renal function (7.9 +/- 2.5 h). Apparent total body clearance was significantly reduced in the renally impaired (25.3 +/- 10.5 ml/min) in relation to the group with normal renal function (48.8 +/- 11.1 ml/min). The first-order absorption rate constants and apparent volumes of distribution did not differ between the two groups. These data indicate that the disposition of roxithromycin is significantly delayed in subjects with CLCRs of less than 15 ml/min and suggest that the roxithromycin dosing interval be doubled for these patients.
对一种研究中的大环内酯类抗生素罗红霉素的处置情况，在20名受试者中进行了评估。其中10名受试者肾功能正常（肌酐清除率[CLCR]为116±17毫升/分钟[平均值±标准差]），另外10名受试者肾功能严重受损（CLCR为10.2±2.6毫升/分钟）。在单次口服300毫克剂量后，利用非线性回归分析，根据一室或二室口服吸收模型对血浆浓度-时间数据进行了分析。与肾功能正常组（7.9±2.5小时）相比，肾功能严重受损组的终末消除半衰期显著延长（15.5±4.7小时）。与肾功能正常组（48.8±11.1毫升/分钟）相比，肾功能受损组的表观全身清除率显著降低（25.3±10.5毫升/分钟）。两组之间的一级吸收速率常数和表观分布容积没有差异。这些数据表明，CLCR低于15毫升/分钟的受试者中罗红霉素的处置明显延迟，提示这些患者的罗红霉素给药间隔应加倍。
