Chapron D J, Sweeney K R, Feig P U, Kramer P A
Br J Clin Pharmacol. 1985 Mar;19(3):363-71. doi: 10.1111/j.1365-2125.1985.tb02655.x.
The disposition kinetics of acetazolamide (AZ) has been studied in four young and four elderly healthy volunteers, each of whom received an intravenous bolus dose of 5 mg/kg. The concentration time profile of AZ was determined in plasma, plasma ultrafiltrate, erythrocytes and urine. While the mean area under unbound plasma concentration-time curves was 81% higher in elderly subjects, areas based on total drug concentrations were similar in both groups. The mean renal plasma clearance was similar in both groups. The mean renal plasma clearance was similar between young and old for total AZ, but was significantly lower in the elderly for unbound drug (8.88 ml min-1 kg-1 vs 15.7 ml min-1 kg-1). Renal clearance of unbound AZ correlated well with creatinine clearance (r = 0.846, P less than 0.01). Peak erythrocyte levels were 45% higher in the elderly group (37.2 micrograms/ml vs 25.3 micrograms/ml) and were paralleled by a 46% increase in the mean area under the erythrocyte concentration-time curve for this age group. The unbound fraction of AZ in plasma was significantly greater in elderly than younger subjects (6.9 vs 4.1%, P less than 0.05). Integrated AZ erythrocyte concentrations correlated positively with AZ free fraction in plasma and inversely with its unbound renal clearance. These observed differences in AZ disposition between elderly and young have served to clarify host factors which may importantly influence susceptibility to adverse effects.
已在4名年轻健康志愿者和4名老年健康志愿者中研究了乙酰唑胺（AZ）的处置动力学，每名志愿者均接受了5mg/kg的静脉推注剂量。测定了血浆、血浆超滤液、红细胞和尿液中AZ的浓度-时间曲线。虽然老年受试者未结合血浆浓度-时间曲线下的平均面积高81%，但两组基于总药物浓度的面积相似。两组的平均肾血浆清除率相似。总AZ的平均肾血浆清除率在年轻人和老年人之间相似，但未结合药物在老年人中的清除率显著较低（8.88ml·min⁻¹·kg⁻¹对15.7ml·min⁻¹·kg⁻¹）。未结合AZ的肾清除率与肌酐清除率密切相关（r = 0.846，P＜0.01）。老年组的红细胞峰值水平高45%（37.2μg/ml对25.3μg/ml），且该年龄组红细胞浓度-时间曲线下的平均面积增加了46%。血浆中AZ的未结合分数在老年人中显著高于年轻人（6.9%对4.1%，P＜0.05）。红细胞中AZ的综合浓度与血浆中AZ的游离分数呈正相关，与未结合肾清除率呈负相关。观察到的老年人和年轻人在AZ处置方面的这些差异有助于阐明可能对不良反应易感性有重要影响的宿主因素。
