Effects of age on serum glucose and insulin concentrations and glucose/insulin ratios in neonatal foals and their dams during the first 2 weeks postpartum.

Maintaining serum glucose concentrations is critical in neonatal foals and is often dysregulated in illness; however, few studies have assessed the effects of age, or variation of glucose and insulin, in neonates and their postpartum dams. This study aimed to serially evaluate serum glucose and insulin concentrations and glucose/insulin (G/I) ratios in seven healthy foals and their dams immediately postpartum and at 1-2 and 10-12days of age. The hypotheses were that: (1) there would be wide temporal variation in hourly glucose and insulin measurements among foals; and (2) measured parameters in foals would differ from those of postpartum mares. Pre-suckle glucose concentrations were lower than post-suckle (5.15±1.61mmol/L and 7.16±3.13mmol/L, respectively, P=0.0377). Glucose remained >5mmol/L but varied hourly by up to 4.22mmol/L and 2.93mmol/L for individual foals 1-2 and 10-12days old, respectively. There were no significant changes in insulin over time (median 8.50 [4.32-18.4]µU/mL, 1-2days old) in foals. The maximum hourly variation of insulin for an individual foal was 7.53µU/mL and 14.78µU/mL (1-2days and 10-12days old, respectively). Glucose/insulin ratios increased from pre- and post-suckle to the 1-2days old period, with no significant changes thereafter. Mares had highest glucose and insulin concentrations and lowest G/I ratios immediately postpartum compared to later time points and to foals (median 7.37 [range, 4.34-8.78]mmol/L, median 30.94 [range, 20.35-49.20]µU/mL, 4.3 [2.43-7.04], respectively). In conclusion, neonatal foals exhibited wide variation in serum glucose and insulin concentrations but were not hypoglycemic. Mares developed transient insulin resistance in the immediate post-partum period.

Triglyceride concentrations in neonatal foals: Serial measurement and effects of age and illness.

Few studies have evaluated the effects of age and illness on serum triglyceride concentrations in neonatal foals. The objectives of this study were to evaluate triglyceride concentrations in neonatal foals and their dams through serial measurement immediately postpartum and at 1-2 days and 10-12 days of age, as well as to measure them in sick foals. Serially measured serum triglycerides in seven healthy foals varied with age. Median (range) triglyceride concentrations were 28mg/dL (12-50mg/dL), 89mg/dL (51-264mg/dL), and 60mg/dL (28-135mg/dL) immediately postpartum, at 1-2 days of age, and 10-12 days of age, respectively (P<0.001). Triglyceride concentrations varied hourly by up to 117mg/dL in individual foals. The dams had lower triglycerides (median, 20mg/dL; range, 12-49mg/dL) than the foals, once foals were >24h old. Sick foals <24h old had lower triglycerides than sick foals aged 1-7 days (median, 41mg/dL [range, 16-116]; median, 110mg/dL [range, 24-379mg/dL]; P<0.001). Age and triglyceride concentration showed a non-linear association independent of foal health status (P=0.01). Sick foals with positive bacterial cultures had higher triglycerides than those with negative cultures (median, 111mg/dL [range, 10-379mg/dL] and median 53mg/dL [range, 17-271mg/dL], respectively; P=0.033). Nonsurvivors had higher triglycerides than survivors (median, 116mg/dL [range, 41-379mg/dL] and median, 55mg/dL [range, 10-311mg/dL], respectively; P=0.04). In conclusion, triglycerides were highest in healthy neonatal foals aged 1-2 days, and in nonsurviving sick foals and those with positive bacterial cultures. Age was associated with triglyceride concentration regardless of health status.

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

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).