Varoquaux O, Lajoie D, Gobert C, Cordonnier P, Ducreuzet C, Pays M, Advenier C
Br J Clin Pharmacol. 1985 Dec;20(6):575-81. doi: 10.1111/j.1365-2125.1985.tb05114.x.
The pharmacokinetics of a co-trimoxazole preparation (Bactrim Forte) containing trimethoprim (TMP) 160 mg and sulphamethoxazole (SMZ) 800 mg were determined in six young adults (29.3 +/- 4.4 s.d. years) and six elderly people (78.6 +/- 6.6 s.d. years). Following oral administration of a single dose, the pharmacokinetic parameters of SMZ and its N4-acetylated metabolite (N4SMZ) were similar in both groups. However Cmax of TMP was greater (2.06 +/- 0.29 s.d. vs 1.57 +/- 0.32 s.d. mg l-1; P less than 0.01) and its area under the curve was larger (34.30 +/- 6.98 s.d. vs 23.87 +/- 3.82 s.d. mg l-1 h; P less than 0.001) in elderly people than in younger subjects. Total clearance (CL/F) of TMP normalized to body weight was not significantly different in the two groups. There was no significant difference in serum protein binding of TMP and SMZ between the two groups. Urinary excretion of TMP, SMZ and N4SMZ was reduced by about 50% in the elderly compared to the young subjects. Renal clearance of TMP was significantly lower in the elderly group (19 +/- 10 s.d. vs 55 +/- 14 s.d. ml h-1 kg-1; P less than 0.001). Renal clearance of SMZ was not significantly different in the two groups. A study of plasma concentrations of TMP, SMZ and N4SMZ during continuous dosing in seven elderly patients treated for urinary or respiratory infections showed that steady state was reached after 3 days of treatment and that plasma drug concentrations were about two to three times higher than those observed after a single dose.
在6名年轻成年人（平均年龄29.3±4.4岁，标准差）和6名老年人（平均年龄78.6±6.6岁，标准差）中测定了含有160毫克甲氧苄啶（TMP）和800毫克磺胺甲恶唑（SMZ）的复方新诺明制剂（复方新诺明强效片）的药代动力学。单次口服给药后，两组中SMZ及其N4-乙酰化代谢物（N4SMZ）的药代动力学参数相似。然而，老年人中TMP的Cmax更高（2.06±0.29，标准差，对比1.57±0.32，标准差，毫克/升；P＜0.01），其曲线下面积更大（34.30±6.98，标准差，对比23.87±3.82，标准差，毫克/升·小时；P＜0.001）。以体重标准化的TMP的总清除率（CL/F）在两组中无显著差异。两组中TMP和SMZ的血清蛋白结合率无显著差异。与年轻受试者相比，老年人中TMP、SMZ和N4SMZ的尿排泄减少约50%。老年组中TMP的肾清除率显著更低（19±10，标准差，对比55±14，标准差，毫升/小时·千克-1；P＜0.001）。两组中SMZ的肾清除率无显著差异。对7名接受泌尿系统或呼吸道感染治疗的老年患者连续给药期间TMP、SMZ和N4SMZ的血浆浓度研究表明，治疗3天后达到稳态，且血浆药物浓度比单次给药后观察到的浓度高约2至3倍。
