Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses

Grady, Jason A.; Davis, Elizabeth G.; KuKanich, Butch; Sherck, Amanda B

doi:10.2460/ajvr.71.7.831

Cited by 35 publications

(50 citation statements)

References 21 publications

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“…This observation is similar to that of prior studies and suggested that the horse is very sensitive to the effects of exogenously administered glucocorticoids (Gylstorff & Hegner, 1983; Soma et al. , 2006; Grady et al. , 2010; Soma et al.…”

Section: Discussionsupporting

confidence: 91%

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Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone

Soma

Uboh

Liu

et al. 2012

Vet Pharm & Therapeutics

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This study investigated and compared the pharmacokinetics of intra-articular (IA) administration of dexamethasone sodium phosphate (DSP) into three equine joints, femoropatellar (IAS), radiocarpal (IAC), and metacarpophalangeal (IAF), and the intramuscular (IM), oral (PO) and intravenous (IV) administrations. No significant differences in the pharmacokinetic estimates between the three joints were observed with the exception of maximum concentration (Cmax ) and time to maximum concentration (Tmax ). Median (range) Cmax for the IAC, IAF, and IAS were 16.9 (14.6-35.4), 23.4 (13.5-73.0), and 46.9 (24.0-72.1) ng/mL, respectively. The Tmax for IAC, IAF, and IAS were 1.0 (0.75-4.0), 0.62 (0.5-1.0), and 0.25 (0.08-0.25) h, respectively. Median (range) elimination half-lives for IA and IM administrations were 3.6 (3.0-4.6) h and 3.4 (2.9-3.7) h, respectively. A 3-compartment model was fitted to the plasma dexamethasone concentration-time curve following the IV administration of DSP; alpha, beta, and gamma half-lives were 0.03 (0.01-0.05), 1.8 (0.34-2.3), and 5.1 (3.3-5.6) h, respectively. Following the PO administration, the median absorption and elimination half-lives were 0.34 (0.29-1.6) and 3.4 (3.1-4.7) h, respectively. Endogenous hydrocortisone plasma concentrations declined from a baseline of 103.8 ± 29.1-3.1 ± 1.3 ng/mL at 20.0 ± 2.7 h following the administration of DSP and recovered to baseline values between 96 and 120 h for IV, IA, and IM administrations and at 72 h for the PO.

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Section: Discussionsupporting

confidence: 91%

“…, 1996). In a more recent study, the pharmacokinetics of oral powder of DXM and suspension were compared with the IV administration (Grady et al. , 2010).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone

Soma

Uboh

Liu

et al. 2012

Vet Pharm & Therapeutics

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“…). The pharmacokinetic parameter estimates in Standardbreds collected in this study are consistent with values previously reported for Thoroughbreds (Cunningham et al ., ; Soma et al ., , ; Grady et al ., ).…”

Section: Discussionmentioning

confidence: 97%

A quantitative approach to analysing cortisol response in the horse

Ekstrand

Ingvast-Larsson

Olsén

et al. 2015

Vet Pharm & Therapeutics

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The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17 μg/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57 μg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 μg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.

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“…11,14,15 Depending on the dose rate, clearance from plasma after intravenous and intramuscular administration has been reported as 48-72 h, 9,12,13 whereas clearance in plasma after intra-articular administration was complete in 5/6 horses by 72 h. 13 There was one horse in the present study that had a plasma concentration of dexamethasone of 0 at 32 h but then registered a reading of 0.1 ng/mL at 96 h. This was unexpected and may have been associated with redistribution of the drug into fat or muscle tissue after nebulisation before being released back into the circulation. Current regulatory recommendations for horses in competition, subjected to blood and/or urine samples, are based on the intravenous, intramuscular or intra-articular administration of a single dose of dexamethasone.…”

Section: Discussionmentioning

confidence: 99%

Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation

et al. 2019

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Objective To quantify the time to clear dexamethasone from plasma and urine of horses following a single nebulisation.Design Experimental using six Standardbred mares.Methods Dexamethasone sodium phosphate (0.04 mg/kg) diluted in 0.9% sodium chloride was administered as an aerosol using a Flexineb E2® nebuliser. Blood samples (0, 2, 4, 6, 8, 10, 12, 24, 32, 48, 72 and 96 h) and urine samples (0, 1, 4, 8, 24, 32, 48, 72 and 96 h) were collected for analysis using liquid chromatography mass spectrometry.Results Maximum plasma concentrations (t max ) were reached by the earliest detection point (2 h) after nebulisation (0.6--1.8 ng/mL), but was no longer detectable at 48 h. However, in one horse 0.1 ng/mL was found at 96 h after three consecutive readings of 0 ng/mL. The t max in urine was reached by the earliest collection point (1 h) after nebulisation (3.2-23.8 ng/mL), but was no longer present in urine at 72 h in five horses, while detectable levels (0.1 ng/mL) were still present at 96 h in one horse.Conclusions A single dose of 0.04 mg/kg of DSP administered as an aerosol through a FlexinebE2® mask was no longer detectable in blood at 48 h in six horses tested, but one horse returned a reading of 0.1 ng/mL at 96 h after having no detectable levels. Dexamethasone was not detectable in urine at 72 h in five horses but was detectable at a low concentration (0.1 ng/mL) at 96 h in one horse.

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Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses

Abstract: PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.

Cited by 35 publications

References 21 publications

Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone

Pharmacokinetics of dexamethasone following intra‐articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone

A quantitative approach to analysing cortisol response in the horse

Pilot study to quantify the time to clear dexamethasone from plasma and urine of adult horses following a single nebulisation

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