Pharmacokinetics of metronidazole in foals: influence of age within the neonatal period

Abstract

Neonatal foals have unique pharmacokinetics, which may lead to accumulation of certain drugs when adult horse dosage regimens are used. Given its lipophilic nature and requirement for hepatic metabolism, metronidazole may be one of these drugs. The purpose of this study was to determine the pharmacokinetic profiles of metronidazole in twelve healthy foals at 1-2.5 days of age when administered as a single intravenous (IV) and intragastric (IG) dose of 15 mg/kg. Foals in the intravenous group were studied a second time at 10-12 days of age to evaluate the influence of age on pharmacokinetics within the neonatal period. Blood samples were collected at serial time points after metronidazole administration. Metronidazole concentration in plasma was measured using LC-MS. Pharmacokinetic parameters were determined using noncompartmental analysis and compared between age groups. At 1-2.5 days of age, the mean peak plasma concentration after IV infusion was 18.79 ± 1.46 μg/mL, elimination half-life was 11.8 ± 1.77 h, clearance was 0.84 ± 0.13 mL/min/kg and the volume of distribution (steady-state) was 0.87 ± 0.07 L/kg. At 10-12 days of age, the mean peak plasma concentration after IV infusion was 18.17 ± 1.42 μg/mL, elimination half-life was 9.07 ± 2.84 h, clearance was 1.14 ± 0.21 mL/min/kg and the volume of distribution (steady-state) was 0.88 ± 0.06 L/kg. Oral approximated bioavailability was 100%. Cmax and Tmax after oral dosing were 14.85 ± 0.54 μg/mL and 1.75 (1-4) h, respectively. The elimination half-life was longer and clearance was reduced in neonatal foals at 1-2.5 days as compared to 10-12 days of age (P = 0.006, P = 0.001, respectively). This study warrants consideration for altered dosing recommendations in foals, especially a longer interval (12 h).

Pharmacokinetics of a sulfadiazine and trimethoprim suspension in neonatal foals

“…Increased total body water of neonatal foals (Fielding et al., 2011) and decreased body fat content (Caprile & Short, 1987; Webb & Weaver, 1979) alter drug disposition in this population. Additionally, the neonatal pharmacokinetic profiles of drugs alter rapidly as the foal matures (Adamson et al., 1991; Swain et al., 2015). Consequently, it is commonly recommended to reduce the dose and dosing frequency to improve the safety when these drugs are used in neonates.…”

Systemic antimicrobial therapy in foals

“…The drug has a longer elimination half‐life in foals compared with adults and should be used at a lower dose (Swain et al . 2014).…”

“…Metronidazole is indicated for the treatment of anaerobic infection including clostridial infections. The drug has a longer elimination half-life in foals compared with adults and should be used at a lower dose (Swain et al 2014).…”