Dexamethasone bovine pharmacokinetics

Gaignage, Ph; Lognay, Georges; Bosson, Danièle; Vertongen, D.; Dreze, P.; Marlier, M.; Séverin, M.

doi:10.1007/bf03189963

Cited by 12 publications

(4 citation statements)

References 5 publications

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“…In a study, the injection of a glucocorticoid (isoflupredone) increased serum NEFA concentration in early postpartum cows (Seifi et al, 2007), whereas a similar, more recent study reported no effect of dexamethasone (Sami et al, 2015). The dexamethasone half-life in bovine plasma is between 5 and 6 h (Toutain et al, 1982;Gaignage et al, 1991). Fairclough et al (1981) showed in dairy cows that the peak plasma concentration of dexamethasone occurred 2 to 20 min after the i.m.…”

Section: Discussionmentioning

confidence: 97%

Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress

Ollier

Beaudoin

Vanacker

et al. 2016

Journal of Dairy Science

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When cows are unable to consume enough feed to support milk production, they often fall into severe negative energy balance. This leads to a weakened immune system and increases their susceptibility to infectious diseases. Reducing the milk production of cows subjected to acute nutritional stress decreases their energy deficit. The aim of this study was to compare the effects on metabolism and immune function of reducing milk production using quinagolide (a prolactin-release inhibitor) or dexamethasone in feed-restricted cows. A total of 23 cows in early/mid-lactation were fed for 5 d at 55.9% of their previous dry matter intake to subject them to acute nutritional stress. After 1 d of feed restriction and for 4 d afterward (d 2 to 5), cows received twice-daily i.m. injections of water (control group; n=8), 2mg of quinagolide (QN group; n=7), or water after a first injection of 20mg of dexamethasone (DEX group; n=8). Feed restriction decreased milk production, but the decrease was greater in the QN and DEX cows than in the control cows on d 2 and 3. As expected, feed restriction reduced the energy balance, but the reduction was lower in the QN cows than in the control cows. Feed restriction decreased plasma glucose concentration and increased plasma nonesterified fatty acid (NEFA) and β-hydroxybutyrate (BHB) concentrations. The QN cows had higher glucose concentration and lower BHB concentration than the control cows. The NEFA concentration was also lower in the QN cows than in the control cows on d 2. Dexamethasone injection induced transient hyperglycemia concomitant with a reduction in milk lactose concentration; it also decreased BHB concentration and decreased NEFA initially but increased it later. Feed restriction and quinagolide injections did not affect the blood concentration or activity of polymorphonuclear leukocytes (PMN), whereas dexamethasone injection increased PMN blood concentration but decreased the proportion of PMN capable of inducing oxidative burst. Incubation of peripheral blood mononuclear cells in serum harvested on d 2 of the restriction period reduced their ability to react to mitogen-induced proliferation, and injection of quinagolide or dexamethasone could not alleviate this effect. This experiment shows that prolactin-release inhibition could be an alternative to dexamethasone for reducing milk production and energy deficit in cows under acute nutritional stress, without disturbing immune function.

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Section: Discussionmentioning

confidence: 97%

Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress

Ollier

Beaudoin

Vanacker

et al. 2016

Journal of Dairy Science

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“…The development of a rapid, simple and accurate analytical method for the determination of drug components in vivo is of great importance in pharmacokinetic studies as well as research on its relationship with pharmacodynamics in specific diseases during the process of drug development. Since the variation between different species may exert an influence on the metabolism of DEX and the xenograft nude mice model is generally used in the studies related to cancer, the pharmacokinetic profile of DEX in nude mice has become essential in its further study as an anticancer drug and its possible combination with other drugs in preclinical studies (Gaignage et al, 1991;Grady et al, 2010;Watteyn et al, 2013). However, to the best of our knowledge, no analytical method for the determination of dexamethasone in nude mice plasma has been established.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a highly sensitive LC‐MS/MS method for the determination of dexamethasone in nude mice plasma and its application to a pharmacokinetic study

Yin

Zhou

et al. 2014

Biomedical Chromatography

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In the current study, a simple, sensitive and rapid analytical method for the determination of dexamethasone was developed and applied to a pharmacokinetic study in nude mice. Using testosterone as an internal standard, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach after one-step precipitation with acetonitrile was validated and used to determine the concentrations of dexamethasone in nude mice plasma. The method utilized a simple isocratic reverse phase separation over a Dionex C18 column with a mobile phase composed of acetonitrile-water (40:60, v/v). The analyte was detected by a triple quadrupole tandem mass spectrometer via electrospray and multiple reaction monitoring was employed to select both dexamethasone at m/z 393.0/147.1 and testosterone at m/z 289.5/97.3 in the positive ion mode. The calibration curves were linear (r >0.99) ranging from 2.5 to 500 ng/mL with a lower limit of quantitation of 2.5 ng/mL. The relative standard deviation ranged from 1.69 to 9.22% while the relative error ranged from -1.92 to -8.46%. This method was successfully applied to a preclinical pharmacokinetic study of dexamethasone and its pharmacokinetics was characterized by a two-compartment model with first-order absorption in female nude mice.

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“…on d −1, 12.40 h prior to heifers undergoing ACTH challenge (Synacthen Ampoules, Novartis Pharmaceutical Ltd., UK) on the following morning (d 0). In cattle, DEX is rapidly absorbed and the elimination half-life of DEX has been reported by Toutain et al to ranges from 291 to 335 min [ 16 , 17 ]. Dexamethasone was administered to equalize systemic concentrations of cortisol [ 9 ] in animals across the RFI groups, in an effort to facilitate a more equitable examination of ACTH on cortisol release [ 18 , 19 ].…”

Section: Methodsmentioning

confidence: 99%

Stress and immunological response of heifers divergently ranked for residual feed intake following an adrenocorticotropic hormone challenge

Kelly

Lawrence

Earley

et al. 2017

J Animal Sci Biotechnol

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BackgroundWhen an animal is exposed to a stressor, metabolic rate, energy consumption and utilisation increase primarily through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Changes to partitioning of energy by an animal are likely to influence the efficiency with which it is utilised. Therefore, this study aimed to determine the physiological stress response to an exogenous adrenocorticotropic hormone (ACTH) challenge in beef heifers divergently ranked on phenotypic residual feed intake (RFI).ResultsData were collected on 34 Simmental weaning beef heifers the progeny of a well characterized and divergently bred RFI suckler beef herd. Residual feed intake was determined on each animal during the post-weaning stage over a 91-day feed intake measurement period during which they were individually offered adlibitum grass silage and 2 kg of concentrate per head once daily. The 12 highest [0.34 kg DM/d] and 12 lowest [−0.48 kg DM/d] ranking animals on RFI were selected for use in this study. For the physiological stress challenge heifers (mean age 605 ± 13 d; mean BW 518 ± 31.4 kg) were fitted aseptically with indwelling jugular catheters to facilitate intensive blood collection. The response of the adrenal cortex to a standardised dose of ACTH (1.98 IU/kg metabolic BW0.75) was examined. Serial blood samples were analysed for plasma cortisol, ACTH and haematology variables. Heifers differing in RFI did not differ (P = 0.59) in ACTH concentrations. Concentration of ACTH peaked (P < 0.001) in both RFI groups at 20 min post-ACTH administration, following which concentration declined to baseline levels by 150 min. Similarly, cortisol systemic profile peaked at 60 min and concentrations remained continuously elevated for 150 min. A RFI × time interaction was detected for cortisol concentrations (P = 0.06) with high RFI heifers had a greater cortisol response than Low RFI from 40 min to 150 min relative to ACTH administration. Cortisol response was positively associated with RFI status (r = 0.32; P < 0.01). No effect of RFI was evident for neutrophil, lymphocytes, monocyte, eosinophils and basophil count. Plasma red blood cell number (6.07 vs. 6.23; P = 0.02) and hematocrit percentage (23.2 vs. 24.5; P = 0.02) were greater for low than high RFI animals.ConclusionsEvidence is provided that feed efficiency is associated with HPA axis function and susceptibility to stress, and responsiveness of the HPA axis is likely to contribute to appreciable variation in the efficiency feed utilisation of cattle.

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Dexamethasone bovine pharmacokinetics

Cited by 12 publications

References 5 publications

Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress

Effect of reducing milk production using a prolactin-release inhibitor or a glucocorticoid on metabolism and immune functions in cows subjected to acute nutritional stress

Development and validation of a highly sensitive LC‐MS/MS method for the determination of dexamethasone in nude mice plasma and its application to a pharmacokinetic study

Stress and immunological response of heifers divergently ranked for residual feed intake following an adrenocorticotropic hormone challenge

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