ABSTRACT
The absolute bioavailability of flumequine after semisimultaneous intramuscular administration as a water-based suspension to veal calves was 92 +/- 14%. The semisimultaneous experimental design provided a reliable determination of absorption rate and demonstrated flip-flop pharmacokinetics. No period or sequence effects were detected. Calculated elimination rate, clearance, and volume of distribution after intravenous administration were comparable to values obtained from traditional design studies. The semisimultaneous experimental design proved to be valuable for the assessment of bioavailability and pharmacokinetics of drugs in food-producing animals while preventing violation of basic clearance assumptions.
Subject(s)
Anti-Infective Agents/pharmacokinetics , Fluoroquinolones , Quinolizines/pharmacokinetics , Animals , Anti-Infective Agents/administration & dosage , Biological Availability , Cattle , Chromatography, High Pressure Liquid , Injections, Intramuscular , Injections, Intravenous , Male , Monte Carlo Method , Quinolizines/administration & dosage , SuspensionsABSTRACT
Mercer et al. (1977) proposed a three-phase experimental design to establish withdrawal times, based on plasma pharmacokinetics. This approach was the premise of a study in which plasma pharmacokinetics and tissue depletion data of oxytetracycline after intramuscular administration were correlated. Correlations between estimated and measured concentrations were shown to be significant for kidney tissue (r = .9236, p < .001), liver tissue (r = .9302, p < .01) as well as for muscle tissue (r = .9045, p < .001). The data presented support the pharmacokinetic approach as proposed by Mercer et al. (1977) and demonstrate that tissue elimination rates correlate highly with elimination rates in plasma. Although generalizations must be applied with caution, this article shows that when certain criteria are fulfilled, plasma pharmacokinetics can reliably predict tissue withdrawal times.
Subject(s)
Cattle/metabolism , Drug Residues/pharmacokinetics , Oxytetracycline/pharmacokinetics , Absorption , Animals , Injections, Intramuscular , Male , Meat/analysis , Models, Biological , Oxytetracycline/administration & dosage , Oxytetracycline/blood , Tissue DistributionABSTRACT
The pharmacokinetics of oxytetracycline were studied after both intravenous (i.v.) and intramuscular (i.m.) administration to a group of five veal calves. Blood samples were taken frequently during the terminal elimination phase in order to calculate a reliable elimination rate constant. Because of the low limit of quantification of the method of analysis used, oxytetracycline plasma concentrations could be monitored over a 12-day period of time. After the intravenous administration of oxytetracycline, data were fitted according a three-compartment model. After i.m. administration, plasma-concentration-time curves could best be described by a two-compartment model. It was demonstrated that a very slow terminal elimination phase was present both after i.v. and i.m. administration with a half-life of approximately 95 h. The data show that this phase cannot be explained by slow absorption from the injection site and that release of oxytetracycline incorporated into bone is not a likely explanation.
