Pharmacokinetics of a sulfadiazine and trimethoprim suspension in neonatal foals

Abstract

There is limited investigation of neonatal foal pharmacokinetic parameters for the antimicrobial combination of sulfadiazine (SDZ) and trimethoprim (TMP). Neonatal pharmacokinetic investigation of the sulfadiazine–trimethoprim combination is required to ensure safe and effective utilization in this population. The purpose of this study was to determine the pharmacokinetics of sulfadiazine–trimethoprim in five healthy neonatal foals with oral administration at 24 mg/kg every 12 hr (hrs) for 10 days. Blood samples were collected at serial time points at approximately 72 hr of age (steady‐state) and at days 5 and 10 to monitor the influence of age within the neonatal period. Pharmacokinetic parameters were determined using a one‐compartment model analysis, and mean ± SD was calculated. Cmax was 37.8 ± 13.4 μg/ml (SDZ) and 1.92 ± 0.25 μg/ml (TMP). Tmax was 1.4 ± 0.6 hr (SDZ) and 1.4 ± 0.4 hr (TMP). Cmin for SDZ and TMP was 16.84 ± 8.46 μg/ml and 0.46 ± 0.24 μg/ml, respectively. Elimination half‐life was 10.8 ± 6.1 hr (SDZ) and 6.5 ± 2 hr (TMP). AUC0 → ∞ was 667 ± 424 μg × hr/ml (SDZ) and 21.1 ± 5.3 μg × hr/ml (TMP). Foals remained healthy, and the plasma concentration of sulfadiazine–trimethoprim reached levels above MIC(90) for Streptococcus equi ssp. (SDZ/TMP): 9.5/0.5 μg/ml).

The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration

“…Both t 1/2 c (2.9 h) and the half‐life of the terminal phase ( t 1/2 β ) (4.2 h) was longer than the 1.6 h terminal half‐life presented previously (Brown et al., 1990). However, it was shorter than the half‐life of 6.5 h presented in a recent study (Swain O'Fallon et al., 2020). In this study five 24 mg/kg doses of a 67 mg/ml TMP/333 mg/ml SDZ formulation were administered per os every 12 h to Quarter horse foals.…”

“…However, it was shorter than the half-life of 6.5 h presented in a recent study (Swain O'Fallon et al, 2020). In this study five 24 mg/kg doses of a 67 mg/ml TMP/333 mg/ml SDZ formulation were administered per os There are several reasons why the pharmacokinetics of drugs can differ between neonates and adult horses (Caprile & Short, 1987;Vaala, 1985).…”

“…However, the PK in neonatal foals may not necessarily be the same as in adult horses (Caprile & Short, 1987; Vaala, 1985). The PK of TMP has been described in neonatal foals after co‐administration with sulphamethoxazole as an IV bolus dose, and limited plasma exposure data were recently published after administration per os in foals (Brown et al., 1990; Swain O'Fallon et al., 2020) However, no published PK data are available for TMP/SDZ after repeated IV administration to neonatal foals. Consequently, there are no quantitative data supporting clinically effective dosage regimens of TMP/SDZ combination in foals with sepsis because the PK of SDZ has, to the best of our knowledge, not been properly described in neonatal foals.…”

“…every 12 h to Quarter horse foals. The SDZ elimination half-life after IV administration was approximately 5 h, compared with 10 h in the study bySwain O'Fallon et al (2020). These foals were 1-1.5 days old at the time of inclusion and were also evaluated at 5 and 10 days of age, respectively.…”

Systemic antimicrobial therapy in foals

“…This means that protocols that are extrapolated from adult dosing may not always be appropriate, especially for young foals. For example, standard oral dosing of trimediazine sulphadiazine at 24 mg/ kg achieved higher plasma levels in 1-to 10-day-old foals than would be achieved in adult horses (Swain O'Fallon et al 2020). The rate of elimination of intravenous chloramphenicol has been shown to increase in foals over the first 6 weeks of life, with more prolonged elimination times in premature foals (Adamson et al 1991).…”