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Multivariate meta-analysis of pharmacokinetic studies of ampicillin trihydrate in cattle

Ronette Gehring BVSc, MMedVet1, Deon van der Merwe BVSc, MSc2, Alice N. Pierce BA3, Ronald E. Baynes DVM, PhD4, Arthur L. Craigmill PhD5, and Jim E. Riviere DVM, PhD6
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  • 1 Center for Chemical Toxicology Research and Pharmacokinetics, Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 2 Center for Chemical Toxicology Research and Pharmacokinetics, Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 3 Environmental Toxicology Extension, Food Animal Residue Avoidance Databank, Department of Environmental Toxicology, University of California, Davis, CA 95616.
  • | 4 Center for Chemical Toxicology Research and Pharmacokinetics, Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.
  • | 5 Environmental Toxicology Extension, Food Animal Residue Avoidance Databank, Department of Environmental Toxicology, University of California, Davis, CA 95616.
  • | 6 Center for Chemical Toxicology Research and Pharmacokinetics, Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

Abstract

Objective—To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies.

Sample Population—Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank.

Procedure—Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters.

Results—A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently.

Conclusions and Clinical Relevance—Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration. (Am J Vet Res 2005;66:108–112)

Abstract

Objective—To investigate the feasibility of using multivariate cluster analysis to meta-analyze pharmacokinetic data obtained from studies of pharmacokinetics of ampicillin trihydrate in cattle and identify factors that could account for variability in pharmacokinetic parameters among studies.

Sample Population—Data from original studies of the pharmacokinetics of ampicillin trihydrate in cattle in the database of the Food Animal Residue Avoidance Databank.

Procedure—Mean plasma or serum ampicillin concentration versus time data and potential factors that may have affected the pharmacokinetics of ampicillin trihydrate were obtained from each study. Noncompartmental pharmacokinetic analyses were performed, and values of pharmacokinetic parameters were clustered by use of multivariate cluster analysis. Practical importance of the clusters was evaluated by comparing the frequency of factors that may have affected the pharmacokinetics of ampicillin trihydrate among clusters.

Results—A single cluster with lower mean values for clearance and volume of distribution of ampicillin trihydrate administered PO, compared with other clusters, was identified. This cluster included studies that used preruminant calves in which feeding was withheld overnight and calves to which probenecid had been administered concurrently.

Conclusions and Clinical Relevance—Meta-analysis was successful in detecting a potential subpopulation of cattle for which factors that explained differences in pharmacokinetic parameters could be identified. Accurate estimates of pharmacokinetic parameters are important for the calculation of dosages and extended withdrawal intervals after extralabel drug administration. (Am J Vet Res 2005;66:108–112)