Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in pigs

Abstract

a b s t r a c tThe pharmacokinetics of dexamethasone (DEX) were investigated after an intravenous (IV) or intramuscular (IM) bolus injection of 0.3 mg/kg bodyweight DEX sodium phosphate in pigs. The plasma concentrations of DEX were determined using a validated high-performance liquid chromatographytandem mass spectrometry (LC-MS/MS) method and the pharmacokinetics were determined by one-compartmental analysis.The mean area under the plasma concentration-time curve and the mean elimination half-life were 133.07 ± 39.59 ng.h/mL and 0.77 h, and 173.24 ± 53.59 ng h/mL and 1.06 h following IV and IM administration, respectively. The volume of distribution and clearance recorded after IV administration were 2.78 ± 0.88 L/kg and 2.39 ± 0.57 L/h kg, respectively.An IM bolus injection of DEX sodium phosphate in pigs resulted in a fast and complete absorption, with a mean maximal plasma concentration of 80.94 ± 21.29 ng/mL at 0.35 ± 0.21 h and a high absolute bioavailability of 131.06 ± 26.05%.Ó 2013 Elsevier Ltd. All rights reserved.Dexamethasone (DEX) is a long-acting synthetic hydrocortisone analogue and is one of the most potent glucocorticoid drugs. It is extensively used in veterinary medicine to treat inflammatory, immunological and allergic disorders (Toutain et al., 1982; EMA, 2004;Ferguson et al., 2009). In livestock, the use of DEX is indicated in inflammatory processes such as mastitis, aseptic laminitis, arthritis and primary ketosis. DEX is also reported to be used as an illegal growth promoter (Courtheyn et al., 2002;Ferguson et al., 2009;Vincenti et al., 2009).In order to improve water solubility, glucocorticoids are often formulated as a phosphate ester prodrug, which rapidly hydrolyses and releases free and active alcohols (Rohdewald et al., 1987; EMA, 2004). The pharmacokinetic (PK) properties of DEX have been previously described in humans and diverse animal species, but not in pigs although it has been approved for treatment of inflammatory and allergic disorders in this species (EMA, 2004).The aim of this study was to determine the PK properties of DEX in pigs. The results will be applied in ongoing research studying the immunomodulatory properties of DEX, either alone or in combination with several antibiotics in a porcine lipopolysaccharide (LPS) inflammation model .The experiment was approved by the Ethical Committee of the Faculty of Veterinary Medicine of Ghent University (EC 2011/156).Six clinically healthy male pigs (Landrace) with a mean bodyweight (BW) of 28.3 ± 3.01 kg were randomly divided in two groups. The animals had free access to feed and drinking water. The experiment was performed as a two-way cross-over design with a wash-out period of 5 days. A bolus of 0.3 mg/kg BW DEX sodium phosphate (DEXA 0.2%, Kela Laboratoria) was injected intravenously (IV) in the ear vein or intramuscularly (IM) in the gluteus muscle via a sterile winged infusion needle (25 G; Micro-flo, Novolab). Blood was collected by venepuncture of the jugular vein into EDTA-coated tubes (Vacutest Kima) before admin...

Pharmacokinetics of deflazacort in rabbits after intravenous and oral administration and its interaction with erythromycin

“…In the present study, bioavailability after oral administration of deflazacort ( F = 87.48%) was high, but this value was lower than to values have been obtained for other glucocorticoids in mammalian species (Wyns et al., ). These results indicate that glucocorticoids show good absorption after extravascular routes of administration.…”

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“…Dexamethasone has been known to improve local anesthetics analgesia under different circumstances. 19,20 In pigs, an intramuscular bolus injection of dexamethasone resulted in a fast and complete absorption and a high absolute bioavailability, 21 which would partly explain the immediate analgesic effect in our population.…”

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