ABSTRACT
The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg-1 ) and oral (100 mg kg-1 ) administration. The plasma concentration-time data of florfenicol were described by an open one-compartment model. The elimination half-life (t1/2 ) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h-1 . The apparent volume distribution (Vd ) was calculated to be 0.86 L kg-1 and the mean residence time (MRTiv ) was 30.2 h. Following oral administration, the maximum plasma concentration (Cmax ) of 55.4 µg mL-1 was reached at 12 h (Tmax ). The absorption constant (ka ) was 0.158 h-1 . The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg-1 , followed by 6 maintenance doses at 18 mg kg-1 /daily could be effective against furunculosis in turbot.
Subject(s)
Aeromonas salmonicida/drug effects , Flatfishes , Furunculosis/prevention & control , Gram-Negative Bacterial Infections/veterinary , Thiamphenicol/analogs & derivatives , Administration, Intravenous/veterinary , Administration, Oral , Animals , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Biological Availability , Dose-Response Relationship, Drug , Flatfishes/metabolism , Furunculosis/microbiology , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Gram-Negative Bacterial Infections/prevention & control , Half-Life , Thiamphenicol/administration & dosage , Thiamphenicol/pharmacokinetics , Thiamphenicol/pharmacologyABSTRACT
Extrusion-spheronization pellets are generally produced with microcrystalline cellulose (MCC) as the principal excipient, giving rise to particles of very high quality. A number of alternative excipients have been proposed and evaluated, mostly other cellulose derivatives (e.g. different grades of Avicel), or mixtures of MCCs and other excipients. In the present study, we evaluated the possible use of starch+agglutinant mixtures as principal excipients for extrusion-spheronization pellets, with the aim of producing pellets with more suitable properties for certain types of release. We first characterized the different excipients in terms of morphometry and basic physical properties. Subsequently, torque-rheometry was used to characterize the rheology of wetted masses of the different excipients and excipient mixtures, with the aim of determining optimal amount of wetting agent (water). We also evaluated the water absorption and water retention capacities of each excipient. In view of the results obtained, we produced pellets with the different starch+agglutinant mixtures (but without drug), and used image analysis to characterize pellet morphology. Our results show that some of the mixtures-notably starch (corn starch or wheat starch)+20% white dextrin-gave high-quality pellets with good size and shape distributions. In addition, the properties of the different materials tested suggest that it may be possible to obtain pellets with very different properties.
