Pharmacokinetics of the trimethoprim‐sulphamethoxazole combination in the elderly

• Published in: British journal of clinical pharmacology Vol. 20; no. 6; pp. 575 - 581
• Main Authors: Varoquaux, O., Lajoie, D., Gobert, C., Cordonnier, P., Ducreuzet, C., Pays, M., Advenier, C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1985; Blackwell Science
• Subjects: Acetylation; Adult; Aged; Aging; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Biological Availability; Blood Proteins - metabolism; Drug Combinations - metabolism; Female; Humans; Kinetics; Male; Medical sciences; Pharmacology. Drug treatments; Protein Binding; Sulfamethoxazole - analogs & derivatives; Sulfamethoxazole - metabolism; Time Factors; Trimethoprim - metabolism; Trimethoprim, Sulfamethoxazole Drug Combination; Human; Drug combination; Pharmacokinetics; Age; Oral administration
• ISSN: 0306-5251; 1365-2125
• 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.