Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland.
Abstract: Pharmacokinetics of dexamethasone and prednisolone were studied in 6 horses given dexamethasone alcohol (IV or IM) or dexamethasone 21-isonicotinate as a solution IV or IM (50 micrograms/kg of body weight), prednisolone 21-sodium succinate IV or IM (0.6 mg/kg of body weight), or prednisolone acetate IM (0.6 mg/kg of body weight). Plasma concentrations were determined using a high-performance liquid chromatographic method. After dexamethasone alcohol (IV) or dexamethasone 21-isonicotinate (IV), the half-life of elimination was similar (53 minutes) for both formulations. After dexamethasone (alcohol and isonicotinate, IM), concentrations were low or nondetected. After prednisolone 21-sodium succinate (IV), the half-life of elimination (99.5 minutes) was significantly (P less than 0.01) longer than that for dexamethasone. After prednisolone 21-sodium succinate (IM), absorption was rapid and bioavailability was high. After prednisolone acetate (IM), absorption was slow and prednisolone was present in plasma for about 7 days. Due to the nonlinearity of prednisolone kinetics, a bioavailability higher than 100% was obtained. The basal plasma hydrocortisone concentration was approximately 70 ng/ml. After dexamethasone (IV or IM), plasma hydrocortisone values decreased after a 2-hour delay and returned to base line after a 3 to 4 day delay. After prednisolone 21-sodium succinate (IV or IM), plasma hydrocortisone decreased immediately (IV) or rapidly (IM) and returned to base line after a 24-hour delay. After prednisolone acetate (IM), plasma hydrocortisone decreased for up to 21 days.
Publication Date: 1984-09-01 PubMed ID: 6497132
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- Comparative Study
- Journal Article
- Adrenal
- Bioavailability
- Biological Half-Life
- Clinical Study
- Corticosteroids
- Dexamethasone
- Equine Health
- High-performance Liquid Chromatography (HPLC)
- Horses
- Hydrocortisone
- Intramuscular Administration
- Intravenous Administration
- Pharmacodynamics
- Pharmacokinetics
- Plasma
- Prednisolone
- Steroids
- Veterinary Medicine
- Veterinary Research
Summary
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The research is focused on examining the pharmacokinetics and how dexamethasone and prednisolone influence the adrenal gland in horses. This involves studying their effects, how they’re absorbed and eliminated, and their bioavailability in the body.
Methodology
- The study involved six horses, all of which were administered different forms and methods of the two drugs; dexamethasone alcohol was given intravenously (IV) or intramuscularly (IM), and prednisolone either in the form of 21-sodium succinate IV or IM, or prednisolone acetate IM.
- The concentration of these drugs in the horses’ plasma was determined using a high-performance liquid chromatographic method, a technique used for separating mixtures of compounds in scientific experiments.
Results
- The study found that the half-life – the rate at which a drug is removed from the body – of dexamethasone, whether in alcohol or 21-isonicotinate forms, was similar (53 minutes) for both methods of administration (IV and IM). However, it was found that the drug’s concentrations were low or non-detectable when administered via IM.
- On the other hand, prednisolone’s half-life was longer, specifically 99.5 minutes when administered as 21-sodium succinate IV. Interestingly, this was found to be significantly longer than that for dexamethasone.
- The study also noted that the rapid absorption and high bioavailability of prednisolone 21-sodium succinate when administered IM, as well as its continued presence in the plasma for about seven days when administered as prednisolone acetate. Due to the nonlinearity of prednisolone kinetics, a bioavailability higher than 100% was obtained.
- Moreover, the impact of both drugs on the concentration of hydrocortisone – a corticosteroid hormone produced by the adrenal gland – in the plasma was monitored. After being administered dexamethasone (either IV or IM), plasma hydrocortisone values fell after a delay of 2 hours and returned to baseline levels after a delay of 3 to 4 days. After prednisolone (21-sodium succinate, IV or IM), plasma hydrocortisone decreased immediately (IV) or rapidly (IM) and returned to base line after a 24-hour delay. With prednisolone acetate (IM), plasma hydrocortisone fell for up to 21 days.
Significance
- The research contributes important knowledge about the pharmacokinetics of dexamethasone and prednisolone and their impacts on the adrenal gland in horses, information that could be essential for the correct administration of these drugs in veterinary medicine.
- It also hints at the discrepancies between the half-lives of the two drugs and the manner of their administration, which can influence their absorption and bioavailability in horses. This is especially pertinent for prednisolone, which was found to remain in the system for up to seven days.
Cite This Article
APA
Toutain PL, Brandon RA, de Pomyers H, Alvinerie M, Baggot JD.
(1984).
Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland.
Am J Vet Res, 45(9), 1750-1756.
Publication
Researcher Affiliations
MeSH Terms
- Absorption
- Adrenal Glands / drug effects
- Animals
- Biological Availability
- Dexamethasone / analogs & derivatives
- Dexamethasone / metabolism
- Dexamethasone Isonicotinate / metabolism
- Dexamethasone Isonicotinate / pharmacology
- Female
- Half-Life
- Horses / metabolism
- Hydrocortisone / blood
- Kinetics
- Male
- Prednisolone / analogs & derivatives
- Prednisolone / metabolism
- Prednisolone / pharmacology
Citations
This article has been cited 10 times.- Videla R, Sommardahl C, Smith J, Schaefer DMW, Cox S. Pharmacokinetics of Orally Administered Prednisolone in Alpacas.. Front Vet Sci 2021;8:745890.
- Ekstrand C, Pettersson H, Gehring R, Hedeland M, Adolfsson S, Lilliehöök I. Prednisolone in Dogs-Plasma Exposure and White Blood Cell Response.. Front Vet Sci 2021;8:666219.
- Song D, Jusko WJ. Across-species meta-analysis of dexamethasone pharmacokinetics utilizing allometric and scaling modeling approaches.. Biopharm Drug Dispos 2021 May;42(5):191-203.
- Held F, Ekstrand C, Cvijovic M, Gabrielsson J, Jirstrand M. Modelling of oscillatory cortisol response in horses using a Bayesian population approach for evaluation of dexamethasone suppression test protocols.. J Pharmacokinet Pharmacodyn 2019 Feb;46(1):75-87.
- Del Sole MJ, Schaiquevich P, Aba MA, Lanusse CE, Moreno L. Plasma and ocular prednisolone disposition after oral treatment in cats.. Biomed Res Int 2013;2013:209439.
- McMaster A, Chambers T, Meng QJ, Grundy S, Loudon AS, Donn R, Ray DW. Real-time analysis of gene regulation by glucocorticoid hormones.. J Endocrinol 2008 May;197(2):205-11.
- Al Katheeri NA, Wasfi IA, Lambert M, Saeed A. Pharmacokinetics and pharmacodynamics of dexamethasone after intravenous administration in camels: effect of dose.. Vet Res Commun 2004 Aug;28(6):525-42.
- Dubois EF, Derks MG, Zwinderman AH, Dekhuijzen PN, Van Boxtel CJ, Schweitzer DH. Distinct actions of prednisolone and dexamethasone towards osteocalcin and eosinophilic cationic protein in assumed clinically equivalent doses: a study in healthy men.. Eur J Clin Pharmacol 2003 Mar;58(11):733-7.
- Pruett JH, Fisher WF, DeLoach JR. Effects of dexamethasone on selected parameters of the bovine immune system.. Vet Res Commun 1987;11(4):305-23.
- Steiss JE, White NA, Bowen JM. Electroacupuncture in the treatment of chronic lameness in horses and ponies: a controlled clinical trial.. Can J Vet Res 1989 Apr;53(2):239-43.
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