Comparison of tiletamine and zolazepam pharmacokinetics in tigers (Panthera tigris) and leopards (Panthera pardus): do species differences account for adverse effects in tigers?

Serious post-operative neurological complications of unknown aetiology are reported in tigers after immobilisation using tiletamine and zolazepam. These complications may arise from the persistent effects of tiletamine or active metabolites of tiletamine or zolazepam. Concentrations of tiletamine, zolazepam and some metabolites were measured using high performance liquid chromatography-mass spectrometry in plasma from captive tigers (n = 8) and leopards (n = 9; an unaffected species, for comparison) during anaesthesia for routine clinical procedures. The zolazepam:tiletamine (Z:T) ratio was calculated. Peak concentrations occurred at 9-33 min and ranged from 83.5 to 379.2 ng/mL for tiletamine and 301.1 to 1239.3 ng/mL for zolazepam after correction for dose by weight. There were no significant differences between tigers and leopards. The Z:T ratio was generally <5 and did not differ between species. In both tigers and leopards, zolazepam metabolism appeared to be primarily via demethylation. There was evidence for hydroxylation in leopards, but much less in tigers than leopards. No major differences between the species in parent pharmacokinetics were identified. The metabolism of tiletamine could not be defined with any degree of certainty for either species.