Sirgo M A, Norris S
Geriatric Drug Development, Glaxo Pharmaceuticals, Research Triangle Park, NC 27709.
DICP. 1991 Mar;25(3):284-8. doi: 10.1177/106002809102500313.
The disposition of drugs in the elderly is particularly relevant with antiinfectives, because this population has an increased risk of infections. Renal function deteriorates with age, yet dosage guidelines for antibiotics that allow for this reduction remain to be established. Ceftazidime, a cephalosporin with enhanced antipseudomonal activity that is eliminated primarily by glomerular filtration, has been evaluated in the elderly. Herein, we review ceftazidime's pharmacokinetic profile and dosing considerations in this population. Several aspects of renal function deteriorate with the normal aging process, including a decreased glomerular filtration rate (GFR). Using serum creatinine concentrations as an estimate of the GFR in the elderly is unreliable; a more reliable way of estimating GFR is the use of inulin or 51Cr-editic acid clearance or calculation from formulas or nomograms based on age, weight, sex, and serum creatinine. From pharmacokinetic studies it was found that the elderly individual without renal disease generally has an increased elimination half-life and decreased clearance of ceftazidime compared with a young person. A positive correlation (r = 0.7-0.95) was shown between ceftazidime clearance and GFR, suggesting that estimates of GFR may be used to determine the ceftazidime dose. In several studies, the trough (after 12 hours) ceftazidime serum concentration exceeded by several fold its minimum inhibitory concentration required to inhibit 90% of organisms for most commonly encountered organisms; efficacy and safety were also confirmed with an every-12-hour regimen. A twice-daily dosage regimen for ceftazidime in elderly patients with normal renal function should be considered based on age-related decreases in renal function and drug elimination.
药物在老年人中的处置情况与抗感染药物尤为相关,因为该人群感染风险增加。肾功能会随着年龄增长而衰退,但针对这种衰退情况的抗生素剂量指南仍有待制定。头孢他啶是一种具有增强抗假单胞菌活性的头孢菌素,主要通过肾小球滤过清除,已在老年人中进行了评估。在此,我们回顾头孢他啶在该人群中的药代动力学特征和给药注意事项。随着正常衰老过程,肾功能的几个方面会衰退,包括肾小球滤过率(GFR)降低。使用血清肌酐浓度来估计老年人的GFR并不可靠;估计GFR更可靠的方法是使用菊粉或51Cr-依地酸清除率,或根据年龄、体重、性别和血清肌酐通过公式或列线图进行计算。从药代动力学研究发现,与年轻人相比,无肾脏疾病的老年人通常头孢他啶的消除半衰期延长且清除率降低。头孢他啶清除率与GFR之间呈正相关(r = 0.7 - 0.95),这表明GFR估计值可用于确定头孢他啶剂量。在多项研究中,对于大多数常见微生物,头孢他啶血清谷浓度(12小时后)超过抑制90%微生物所需最低抑菌浓度数倍;每12小时给药方案的疗效和安全性也得到了证实。基于与年龄相关的肾功能减退和药物消除情况,对于肾功能正常的老年患者,应考虑头孢他啶每日两次的给药方案。