Singu Bonifasius S, Mubita Mwangana, Thikukutu Moses M, Mufenda Josef K, McKenzie Shonag B, Verbeeck Roger K
School of Pharmacy, University of Namibia, Windhoek, Namibia.
Windhoek Central Hospital and Katutura Intermediate Referral Hospital, Windhoek, Namibia.
Int J Clin Pharm. 2018 Jun;40(3):520-525. doi: 10.1007/s11096-018-0626-8. Epub 2018 Mar 28.
Background Therapeutic drug monitoring is frequently used to optimize the gentamicin dose. Objective The study investigated whether a 240 mg once daily standard dose achieves the recommended target serum gentamicin concentrations. Setting The prospective, observational study took place in the 2 major public hospitals in Namibia. Method Twenty-nine female patients receiving a standard dose (240 mg gentamicin once daily) participated in the study. Two blood samples were withdrawn to estimate gentamicin pharmacokinetic parameters. Serum creatinine was used to calculate creatinine clearance with the Cockcroft-Gault formula (CL), and estimate glomerular filtration rate (eGFR) by the Modified Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Main outcome measure The outcome measure was the proportion of patients receiving 240 mg gentamicin once daily having C values above 15 mg/L. Results Total body weight (TBW) and body mass index were highly variable: 43-115 kg, and 17.3-41.3 kg/m, respectively. The gentamicin dose normalized for TBW (adjusted body weight for obese patients) was relatively low, i.e. 4.2 ± 0.8 mg/kg (mean SD). Gentamicin C was 14.4 ± 4.7 mg/L; only 9 patients (31%) had a C > 15 g/mL. eGFR (MDRD-4) correlated well with CL, but eGFR (EPI-CKD) formula showed systematic deviations from CLcr. Conclusions (1) a standard 240 mg dose results in gentamicin C values below 15 mg/L in the majority of the patients, (2) eGFR formulas to estimate kidney function will have to be evaluated for their usefulness in the Namibian patient population.
背景 治疗药物监测常用于优化庆大霉素剂量。目的 本研究调查每日一次240mg的标准剂量是否能达到推荐的血清庆大霉素目标浓度。地点 这项前瞻性观察性研究在纳米比亚的两家主要公立医院进行。方法 29名接受标准剂量(每日一次240mg庆大霉素)的女性患者参与了本研究。采集两份血样以估算庆大霉素的药代动力学参数。采用Cockcroft-Gault公式(CL)计算血清肌酐以得出肌酐清除率,并通过肾病改良饮食(MDRD)和慢性肾脏病流行病学协作组(CKD-EPI)方程估算肾小球滤过率(eGFR)。主要结局指标 结局指标是每日一次接受240mg庆大霉素治疗的患者中C值高于15mg/L的比例。结果 总体重(TBW)和体重指数变化很大,分别为43 - 115kg和17.3 - 41.3kg/m²。根据TBW(肥胖患者的调整体重)标准化后的庆大霉素剂量相对较低,即4.2±0.8mg/kg(均值±标准差)。庆大霉素C为14.4±4.7mg/L;只有9名患者(31%)的C>15μg/mL。eGFR(MDRD-4)与CL相关性良好,但eGFR(EPI-CKD)公式与肌酐清除率(CLcr)存在系统性偏差。结论 (1)标准的240mg剂量使大多数患者的庆大霉素C值低于15mg/L,(2)估算肾功能的eGFR公式在纳米比亚患者群体中的实用性有待评估。