Pharmacokinetics and metabolic effects of triamcinolone acetonide and their possible relationships to glucocorticoid-induced laminitis in horses

French, K. R.; Pollitt, Christopher C.; Pass, Michael A.

doi:10.1046/j.1365-2885.2000.00288.x

Cited by 69 publications

(83 citation statements)

References 11 publications

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“…The latter finding is in accord with the suggestion that insulin has a rapid, detrimental effect on the lamellar tissues. It has been hypothesized that decreased glucose metabolism due to insulin resistance might be the most important stage in the pathogenesis of laminitis (French et al 2000) perhaps mediated via disturbances in vascular function (de Laat et al 2010). As a consequence, in horses suffering from PPID it seems important to reduce insulin resistance, thereby potentially decreasing the risk of laminitis as being a major complication of the disorder.…”

Section: Discussionmentioning

confidence: 99%

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Klinkhamer

Menheere

Kolk

2011

Veterinary Quarterly

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Background: Glucocorticoids are suggested to precipitate laminitis and induce insulin resistance in horses. Hypothesis/Objectives: To assess insulin sensitivity and the basal amount of glucose metabolized in equine pituitary pars intermedia dysfunction (PPID). Animals and methods: The euglycaemic hyperinsulinaemic clamp (EHC) technique was performed in seven horses with a diagnosis of PPID based on the presence of hypertrichosis and positive dexamethasone suppression-test results comprising one gelding and six mares with a mean age of 21.1 AE 5.8 (SD; range 15-34) years. Results were compared with those from five negative (healthy) controls comprising two geldings and two mares with a mean age of 10.0 AE 2.5 (range 7-13) years and six positive (diseased) controls comprising two geldings and four mares with a mean age of 12.5 AE 4.5 (range 8-21) years examined during the same period. Differences were assessed by means of the Mann-Whitney U test. Results: Mean basal rate of glucose metabolism (9.0 AE 4.2 versus 16.0 AE 5.2 mmol/kg BW/min; p ¼ 0.030) and mean glucose metabolism rate-to-plasma insulin concentration ratio (2.9 AE 1.6 versus 6.2 AE 2.7 Â 10 À6; p ¼ 0.048) were significantly lower in PPID horses than in negative controls, respectively. No differences were found between both control groups. Conclusions and clinical importance: In horses suffering from PPID it seems important to reduce the insulin resistance, thereby potentially decreasing the risk of laminitis as being a major complication of equine PPID. Plasma glucose concentration following fasting might be considered in the screening of horses for PPID.

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Section: Discussionmentioning

confidence: 99%

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Klinkhamer

Menheere

Kolk

2011

Veterinary Quarterly

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“…Glucocorticoid (cortisol) excess has been theorized to contribute to the development of ID in some animals with PPID or EMS 7, 8, 9. Both short and long‐term experimental administration of synthetic glucocorticoids such as dexamethasone or triamcinolone can decrease insulin sensitivity and cause hyperinsulinemia in healthy horses 10, 11, 12, 13. Ponies with hyperlipidemia (common in EMS1) or PPID and presumptive ID also had increased urinary corticoids reflective of increased circulating cortisol 14…”

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confidence: 99%

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Hart

Wochele

Norton

et al. 2016

Veterinary Internal Medicne

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BackgroundIncreased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders.Hypotheses(1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS).AnimalsFifty‐seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20).MethodsProspective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age‐ and season‐matched controls with t‐tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group.ResultsFree cortisol concentrations were increased in overweight/obese controls (0.3 ± 0.1 μg/dL) compared to lean controls (0.2 ± 0.1 μg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 ± 5.8 μg/dL, P = .005) or ID (8.8 ± 10.2 μg/dL, P = .039) than controls (5.0 ± 0.9 μg/dL), but total cortisol concentrations were similar (P ≥ .350) (PPID: 4.2 ± 4.3 μg/dL; ID: 5.0 ± 4.5 μg/dL; controls: 4.6 ± 1.7 and 5.1 ± 2.1 μg/dL).Conclusions and Clinical ImportanceIncreased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol‐binding capacity could be a component of these endocrine disorders in horses.

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“…injection (0 . 2 mg/kg) and the data were not sufficient for pharmacokinetic analysis (French et al 2000).…”

Section: Resultsmentioning

confidence: 97%

Comparison of the hypothalamic–pituitary–adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation

Abraham

Demiraj

Ungemach

2006

Journal of Endocrinology

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The effects of single injections of glucocorticoid (GC) depot suspension and of long-acting GC were studied in conscious dogs. Both the depot suspension GC triamcinolone-16,17-aacetonide (TAA) and the long-acting triamcinolone acetonide-21-dihydrogen phosphate (TAA-DHP) decreased basal and ACTH-stimulated cortisol levels and in a specific timedependent way. Before treatment, all dogs had normal basal and peak cortisol responses to ACTH challenge (13-15 and O120 nmol/l at 1 h respectively). Intravenous TAA-DHP reduced cortisol levels for 12 h, i.m. TAA reduced cortisol levels as of 1 . 5 h and the effect lasted for at least 4 weeks. Both treatments blunted the peak response to ACTH. ACTH elevated cortisol levels to or above baseline values within 10 days following TAA-DHP treatment, but the TAA treatment suppressed an ACTH response for at least 4 weeks. Kinetic analysis of both the preparations demonstrated rapid absorption (t max , 0 . 6-1 . 5 h) and low maximum plasma concentrations (peak C max , 2 . . 51 nmol/l) of the steroids; indeed, the terminal half-life of TAA-DHP (13 . 9G1 . 3 h) was very much shorter than that of TAA (125 . 9G15 . 8 h). In addition, the mean residence time differed very much (11 vs 160 h for TAA-DHP and TAA respectively), in line with a delayed elimination of the depot compared with the long-acting formulation. Application of these TAA formulations needs careful evaluation for their surprisingly different effects on endocrine stress axis activity.

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Pharmacokinetics and metabolic effects of triamcinolone acetonide and their possible relationships to glucocorticoid-induced laminitis in horses

Cited by 69 publications

References 11 publications

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Basal glucose metabolism and peripheral insulin sensitivity in equine pituitary pars intermedia dysfunction

Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses

Comparison of the hypothalamic–pituitary–adrenal axis susceptibility upon single-dose i.m. depot versus long-acting i.v. triamcinolone acetonide therapy: a direct pharmacokinetic correlation

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