Pharmacokinetics of Co-Trimazine (Sulphadiazine plus Trimethoprim) in Geriatric Patients

Abstract

The study was aimed at analyzing the pharmacokinetics of sulphadiazine (SDZ) and trimethoprim (TMP) in geriatric patients and was carried out in two stages. The first stage compared 11 geriatric patients (68–89 years old) and 9 healthy volunteers (21–34 years old). Serum concentration and urine elimination were determined on day 4 after 12-hourly administration of 1 tablet of co-trimazine containing 410 mg sulphadiazine (SDZ) plus 90 mg trimethoprim (TMP). The mean serum concentrations of SDZ were significantly higher in the older subjects than in the volunteers after 1, 8 and 12 h (p < 0.05, 0.01, 0.01), but were not differentiable after 2 or 4 h. For TMP, the serum levels were higher (p < 0.05) in the patients only after 8 h. The amounts collected in urine were higher in the normal volunteers for SDZ during the intervals 0–2 h (p < 0.05), 2–4 h (p < 0.01), and 4–8 h (p < 0.01), but not for 8–12 h. The 12-hour recovery was 69% SDZ + acetyl-SDZ recovered in the patients compared to 66.0% in the volunteers. Indistinguishable amounts of TMP were recovered during each interval in the two groups of subjects, 59.2% in the patients compared to 70.0% in the volunteers. The second stage of the study comprised 9 geriatric patients of mean age 83.6 years and creatinine clearance 59.2 ml/min who were followed for 11 days. A steady increase in serum levels was observed. The mean peak serum concentration for SDZ was 16.7 ± 4.2 mg/l after the first dose and 44.7 ± 11.3 mg/l on day 10. For acetyl-SDZ, the respective concentrations were 2.1 ± 0.9 and 7.1 ± 3.1 mg/l. TMP rose from 0.79 ± 0.19 mg/l on the first day to 2.8 ± 1.3 mg/l on day 10. Parallel increases in urine elimination of SDZ, acetyl-SDZ and TMP were observed over the 11 days. After the first dose, the 12-hour urine elimination of SDZ corresponded to 16.2% of the dose, that of acetyl-SDZ to 7.5% and of TMP 21.5%. After the final dose, the respective 48-hour values were 103.2, 51.2 and 115%. The t_½ was 16.2 ± 5.6 h for SDZ, 25.5 ± 12.3 h for acetyl-SDZ, and 14.0 ± 6.0 h for TMP.

Antimicrobial Therapy for the Elderly Patient

“…There is information on the pharmacokinetics of various forms of sulfonamides in older subjects; this information was recently reviewed by Ljungberg et al 232 Their review included studies on sulfamethizole, sulfisoxazole, sulfisomidine, sulfadimidine, and sulfadiazine, but not sulfamethoxazole 232 . In a study by Bergan et al, the pharmacokinetics of trimethoprim plus sulphadiazine (sulfadiazine) was investigated in geriatric patients 233 . Their data showed that in older patients TMP serum concentrations were slightly higher and urine excretion was less in comparison with those of young volunteers; the sulfadiazine kinetics were similar.…”