Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals.

The research article focused on assessing differences in cortisol production and metabolism between adult horses and neonatal foals. The study observed that neonatal foals have a higher daily cortisol production rate and distinctive hydrocortisone pharmacokinetics, which might be associated with lower plasma protein binding of cortisol compared to adult horses. This phenomenon may impact cortisol availability during prolonged critical illness in neonatal foals.

Methods

• The study involved ten healthy full-term foals, only 2 to 4 days old, and seven healthy adult horses. Blood samples were obtained every 15 to 20 minutes for a span of 24 hours to find the 24-hour mean cortisol concentration.
• The horses then received an intravenous (i.v.) dose of dexamethasone, a substance used to suppress endogenous (internal) cortisol production.
• Twelve hours after the dexamethasone administration, a swift i.v. bolus of hydrocortisone sodium succinate was administered, and blood samples were taken consecutively to examine hydrocortisone pharmacokinetics – how the body absorbs, distributes, metabolizes, and excretes the drug.

Results

• The average 24-hour cortisol concentration was identified to be significantly lower in neonatal foals (20 ± 4 ng/mL) compared to adult horses (26 ± 6 ng/mL).
• However, the daily cortisol production rate was considerably higher in foals (6,710 ± 320 ng/kg/day) than in horses (2,140 ± 400 ng/kg/day).
• In terms of hydrocortisone pharmacokinetics, foals displayed a notably higher volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h). Conversely, they demonstrated a significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively).

Conclusions

• There are significant differences in cortisol production and metabolism between neonatal foals and adult horses. These differences are consistent with lower plasma protein binding of cortisol in foals.
• The decrease in plasma protein binding could contribute to cortisol insufficiency during long-lasting critical illness in neonatal foals, potentially posing a threat to their health.