Intestinal concentrations of enrofloxacin after different dosage regimens in broiler chickens

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In vivo metabolism of ibuprofen in growing conventional pigs : a pharmacokinetic approach

The juvenile conventional pig has been suggested as a preclinical animal model to evaluate pharmacokinetic (PK), pharmacodynamic (PD), and safety parameters in children. However, a lot of developmental changes in pig physiology still need to be unraveled. While the in vitro ontogeny of pig biotransformation enzymes is getting more attention in literature, the in vivo developmental changes have not yet been investigated. Therefore, the aim of the current study was to evaluate the biotransformation of ibuprofen (IBU) in conventional pigs aged 1 week, 4 weeks, 8 weeks, and 6-7 months after a single intravenous and oral administration of 5 mg/kg body weight (BVV) of IBU, using a PK approach in a crossover design for each age group. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated to determine 2-hydroxyibuprofen (2OH-IBU), carboxyibuprofen (COOH-IBU), and ibuprofen glucuronide (IBU-GICA) in pig plasma. All three metabolites could be quantified in plasma and the following PK parameters were determined: C-max, T-max, AUC(0 -> 6h), area under plasma concentration-time curve (AUC) ratio between parent drug and metabolite, and the absolute oral bioavailability of the parent drug IBU. The plasma concentrations of the metabolites were always lower than those of IBU. The bioavailability was high, indicating limited pre-systemic biotransformation. The AUC ratio of 2OH-IBU and COOH-IBU/IBU showed a significant increase at 4 weeks of age compared to the 1-week-old and 6- to 7-month-old pigs. Interestingly, the IBUGIcA/IBU AUC ratio did not change with age. The present study demonstrated that the main metabolites of IBU in human are also present in growing pigs. The oxidative phase I metabolism of IBU in growing conventional pigs did change with age. In contrast, age did not seem to affect the glucuronidation capacity of IBU in conventional pigs, although more studies with other substrate drugs are needed to confirm this

Pharmacokinetics of dexamethasone in broiler chickens

Dexamethasone (DEX) is a synthetic derivate of cortisol and is one of the most potent glucocorticoids in man and animal. It is well known as an anti-inflammatory drug in many species. In poultry, however, data on the use of DEX are scarce. DEX would be a possible candidate-drug to influence mediators like cytokines and acute phase proteins in a lipopolysaccharide (LPS) inflammation model. First of all, it is important to determine the pharmacokinetics to investigate the immunomodulating properties of this drug. Data on disposition of DEX in broilers are unknown. The aim of this study was to investigate several pharmacokinetic parameters (area under the curve, AUC; absorption and elimination rate constant, kabs and kel; half-life of absorption and elimination, t1/2abs and t1/2el; volume of distribution, Vd; clearance, Cl; maximum plasma concentration at 0 h; maximum plasma concentration, Cmax; time to Cmax, Tmax and absolute bioavailability, F) of DEX in broiler chickens. The DEX experiment was performed as a two-way cross-over design, each group containing three 4-week-old broiler chickens and with a wash-out period of 96 hours. The animals received a bolus of 0.3 mg/kg body weight DEX intravenously (IV) in the wing vein or intramuscularly (IM) in the pectoral muscle. Blood (1 ml) was sampled by venipuncture from the leg vein before (time 0) and post-administration (0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 hours). Plasma was stored at ≤ -15°C until analysis. Quantitation of DEX in plasma was carried out using in-house developed and validated LC-MS/MS methods. The pharmacokinetic parameters were analyzed using WinNonlin, version 6.2.0 (Pharsight). The pharmacokinetics of DEX were analyzed according to a one-compartmental model (see Table 1). After IM administration, the maximum plasma concentration was reached fast at 0.37 h. In contrast to many other species, t1/2el of the corticosteroid was very short. The clearance in chickens was 1.26 L/h.kg, which is higher than for mammals. The Vd amounted to 1 L/kg and is equal to values found in other species. In chickens, a bioavailability of 100% after IM administration of DEX could be calculated, indicating a complete absorption of the drug. The pharmacokinetics hereby presented, will be very useful in an in-house developed LPS-inflammation model in broiler chickens