Pharmacokinetics and tissue residues of Telazol (R) in free-ranging polar bears

A pharmacokinetic and tissue residue study was conducted to assess the risk s associated with human consumption of polar bears in arctic Canada that ha ve been exposed to the immobilizing drug Telazol(R), a mixture of tiletamin e hydrochloride and zolazepam hydrochloride. Twenty-two bears were remotely injected with about 10 mg/kg of Telazol(R). Following immobilization, seru m samples were collected serially at regular intervals until the bears awak ened. Sixteen of the bears were relocated and killed under permit by local hunters at various times from 0.5 to 11 days after dosing. Serum, kidney, m uscle and adipose tissue samples were collected immediately after death. Al l samples were stored at -70 C until analysis by HPLC. The concentration-ti me data of tiletamine and zolazepam in serum during the immobilization peri od were fitted to curves by computer and the pharmacokinetic parameters ass essed. In addition, the serum and tissue samples collected at the time of d eath were analyzed for both parent drugs, for one metabolite of tiletamine (CI-398), and for three metabolites of zolazepam (metabolites 1, 2 and 4). A one-compartment model with first-order absorption and elimination best fi t the time-series data for the drugs in serum during the immobilization per iod. This model gave half-lives (mean +/- SE) for tiletamine and zolazepam of 1.8 +/- 0.2 h and 1.2 +/- 0.08 h, respectively, clearance values of 2.1 +/- 0.3 1.h(-1).kg(-1) and 1.1 +/- 0.1 1.h-(1).kg(-1), and volumes of distr ibution of 5.2 +/- 0.6 1/kg and 1.8 +/- 0.2 1/kg. The concentrations of bot h drugs and their metabolites declined rapidly to trace levels by 24 h post -dosing, although extremely low concentrations of some metabolites were enc ountered sporadically over the entire sampling period. In particular, zolaz epam metabolite 2, remained detectable in fat and muscle tissue at the end of the study, 11 days after dosing. It was concluded that during immobiliza tion, both tiletamine and zolazepam levels decline rapidly in a monoexponen tial fashion, and their pharmacokinetic parameters in polar bears are simil ar to those observed in other species. Tissue levels of the drugs and their metabolites declined sufficiently rapidly that individuals eating meat fro m exposed bears would be unlikely to experience pharmacological effects fro m the drugs. Nevertheless, slight exposure to the drugs and/or their metabo lites might be possible for an indeterminate time after dosing.