Pharmacokinetics of the trimethoprim‐sulphamethoxazole combination in the elderly.

Abstract

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.

Trimethoprim and Sulfamethoxazole Transmembrane Clearance during Modeled Continuous Renal Replacement Therapy

“…Using published TMP pharmacokinetic parameters of CLtb 1.47 ml/min/kg (CLr = 0.79 ml/min/kg and CLnr = 0.68 ml/min/kg) and Vd 1.54 l/kg [15,16,17], TMP 15 mg/ kg/​day administered q6h to a healthy 70 kg individual resulted in modeled steady-state peak and trough concentrations of 7.9 and 6.1 mg/l (fig. 1, 2).…”

“…We identified pharmacokinetic studies that quantified renal clearance (CLr) and total body clearance (CLtb) in addition to other pharmacokinetic parameters to facilitate estimation of TMP/SMX doses for CRRT [15,16,17]. The mean value of TMP/SMX CLtb, CLr, and Vd from these studies were used to predict TMP/SMX concentrations at a steady state with a one-compartment pharmacokinetic model, a model used previously to describe TMP/SMX disposition [13,18].…”

Pharmacokinetic Evaluation of Sulfamethoxazole at 800 Milligrams Once Daily in the Treatment of Tuberculosis

“…The study was approved by the medical ethical committee (METc 2013/195) and registered at ClinicalTrials.gov (NCT01832987). The patients in the study received co-trimoxazole in addition to their standard TB treatment (rifampin, isoniazide, pyrazinamide, or ethambutol) in a dose of 960 mg orally for 4 to 6 days (in order to prevent blood sampling during weekends) to reach steady state, since the half-life is approximately 10 h (22).…”

“…Blood samples were collected before administration and at 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, and 24 h after co-trimoxazole administration after at least 4 days of treatment (i.e., at steady state) (22,23).…”

Efficacy of Iclaprim against Wild-Type and Thymidine Kinase-Deficient Methicillin-Resistant Staphylococcus aureus Isolates in an In Vitro Fibrin Clot Model

“…The protein binding of iclaprim, TMP, and vancomycin to human or rat serum was described to be ca. 90, 50, and 50%, respectively (20,29,35). Growth medium prewarmed to 37°C was inoculated with a final concentration of 10 6 CFU/ml from an overnight culture in TSB and then incubated in a water bath at 37°C with aeration.…”