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


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


METHODS
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
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.
Gehring
Ronette
R
Center for Chemical Toxicology Research and Pharmacokinetics, Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
van der Merwe
Deon
D
Pierce
Alice N
AN
Baynes
Ronald E
RE
Craigmill
Arthur L
AL
Riviere
Jim E
JE
D000667:Ampicillin / Q000493:pharmacokinetics*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002417:Cattle / Q000378:metabolism*; D016000:Cluster Analysis; D015999:Multivariate Analysis
D000900:Anti-Bacterial Agents; D000667:Ampicillin