Pharmacokinetics of the trimethoprim‐sulphamethoxazole combination in the elderly.

British Journal of Clinical Pharmacology - Tập 20 Số 6 - Trang 575-581 - 1985
O Varoquaux, D. Lajoie, C. Gobert, P Cordonnier, C. Ducreuzet, M Pays, C Advenier

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

10.1093/infdis/128.Supplement_3.S584

10.1007/BF01639017

10.2165/00003088-197601040-00003

10.1056/NEJM198205063061804

10.1093/infdis/128.Supplement_3.S547

10.1007/978-1-349-03813-8_7

10.1159/000221272

O'Malley K., 1981, Effect of age and sex on human drug metabolism, Br. med. J., 3, 507

10.2165/00003088-198005050-00001

10.1007/BF01639009

10.1159/000220701

10.1016/S0378-4347(00)84422-9

10.1093/infdis/128.Supplement_3.S556

10.1002/jps.2600680419

Thông tin
Thông tin xuất bản

British Journal of Clinical Pharmacology

Tập 20 Số 6

575-581

Thông tin tác giả