Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals.
OBJECTIVE
To compare daily endogenous cortisol production rate and the pharmacokinetics of an i.v. bolus of hydrocortisone between neonatal foals and adult horses.


METHODS
10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses.


METHODS
Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered i.v. to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid i.v. bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals.


RESULTS
The mean ± SD 24-hour cortisol concentration was significantly lower in foals (20 ± 4 ng/mL) than in horses (26 ± 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 ± 320 ng/kg/d) than in horses (2,140 ± 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than did horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively).


CONCLUSIONS
Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. khart4@uga.edu
Kelsey A
KA
Hart
Levent
L
Dirikolu
Duncan C
DC
Ferguson
Natalie A
NA
Norton
Michelle H
MH
Barton
D017677:Age Distribution; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D005260:Female; D006736:Horses / Q000097:blood*; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D007124:Immunoenzyme Techniques / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007700:Kinetics; D008297:Male; D017711:Nonlinear Dynamics
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone