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Antimicrobial treatment regimens are generally based on pharmacokinetic analysis established in healthy animals. Likewise, in food animals, antimicrobial withdrawal times are based on pharmacokinetic data from healthy animals. In clinical practice, antimicrobials are therapeutically used in disease challenged animals. There is limited literature addressing the question of pharmacokinetic changes in diseased animals. Considering swine, there are approximately 17 searchable peer reviewed studies addressing disease influence on antimicrobial pharmacokinetics. Across those studies there are about 28 diseaseantimicrobial interactions evaluated, of which 21 find that disease changes the pharmacokinetics of the evaluated antimicrobial. None of the current studies address the influence vaccination may have on preserving antibiotic pharmacokinetics in the face of disease challenge.
Original research was performed to evaluate the pharmacokinetics of ceftiofur crystalline free acid in pigs vaccinated against, challenged with, or vaccinated against and challenged with PRRSv. The original research hypothesized that PRRSv wild-type challenge would change pharmacokinetics and previous vaccination would have no effect on pharmacokinetic variables. Previous research had shown ceftiofur pharmacokinetics change with PRRSv infection. The PRRSv vaccine investigated is a commonly used and commercially available modified live virus. The present work found that a wild-type PRRSv infection resulted in a lower AUC0-last, higher Cl/F and higher Vz/F. The present work also determined that the modified live virus used for vaccination did not result in any pharmacokinetic changes, and vaccination with the modified live virus prevented pharmacokinetic changes in pigs that were subsequently challenged with a wild-type virus.
Disease or infection of a virulent organism does not always change antimicrobial pharmacokinetics. Pharmacokinetic changes seem dependent on specific antimicrobial and specific organism. Available research demonstrates PRRSv infection does change pharmacokinetics of ceftiofur drugs. Original research reported in this thesis suggests a modified live PRRSv vaccination has the potential to prevent ceftiofur pharmacokinetic changes that occur in the face of a wild-type PRRSv challenges. This information may be clinically applied by following labeled pharmacokinetic analysis of ceftiofur crystalline free acid in pigs vaccinated with a modified live PRRSv, regardless of wild-type PRRSv challenge.