A Fatality Related to the Veterinary Anesthetic Telazol - Journal of ...

Journal of Analytical Toxicology, Vol. 23, October 1999
preparation were the same. The methods differ only in their
respective column washes and elution solvents. Zolazepam
showed a good response at the lowest calibration level, so the
differences in column wash and elution solvent did not appear to
be significant.
Limit of detection, limit of quantitation, and linearity studies
were not done. The calibration curves were linear with coeffi-
cients of correlation (r 2) of 1.00 and 0.999 for tiletamine and
zolazepam, respectively. The samples were run at dilutions that
fell within the upper and lower calibrators. The sole exception
was the liver zolazepam results.
Postmortem blood, urine, and liver concentrations of tile-
tamine, zolazepam, and ketamine are listed in Table I. Data
regarding toxic human dosages of Telazol are nonexistent.
Although there is a preponderance of veterinary data regarding
dosages required for chemical restraint and surgical anesthesia
of various animal species, it is difficult to correlate these data to
humans. Among the nonhuman primates most closely related to
humans, chimpanzee, orangutan, and gorilla, dosages required
for chemical restraint were 3.63 mg/kg, 2.72 mg/kg, and 1.35
mg/kg, respectively. (7) According to an article by Eads (7), larger
species of primates required smaller doses of Telazol on a weight
basis to produce equivalent results.
Tiletamine belongs to the same class of drugs as ketamine and
phencyclidine. In most respects the pharmacokinetics of these
drugs are the same. In terms of potency, tiletamine is between
ketamine and phencyclidine with ketamine being the weakest
and phencyclidine the most potent. (3) The usual intravenous
dose of ketamine required for induction of anesthesia ranges
from 1 to 4.5 mg/kg. (8) A dose of 2.5 mg/kg resulted in an
average plasma concentration of I IJg/mL after 12 rain, which fell
to 0.5 IJg/mL after 30 rain. (9) Phencyclidine intoxication is
associated with blood levels of 0.007-0.240 IJg/mL. (10) The
usual intravenous dose of PCP was 1-3 rag. (11) Toxic concen-
trations of phencyclidine range from 0.3 to 25 ~g/mL in the
plasma. (8) The deceased had 1000 mg of tiletamine available to
him, which would result in a dose of 9.6 mg/kg if taken all at
once. A dose of 8.25 mg/kg was fatal to a gorilla after 5 h with
death due to respiratory depression. (7) The blood concentra-
tions of tiletamine and zolazepam suggest that it is probable the
decedent did not take the full dose available at one time.
The deceased also took ketamine. Although the postmortem
blood concentration of ketamine was low, 37 ng/mL, ketamine
and tiletamine are the same class of compound, and at least an
additive effect can be assumed.
Assessing the role of zolazepam as a causative agent in this
death is much more difficult. According to an article by Lin et al.
(3), zolazepam was the least likely to cause depression when
compared with chlordiazepoxide and diazepam, which is why it
was chosen in the development of Telazol. Chlordiazepoxide and
diazepam are the two most commonly used benzodiazepines in
veterinary medicine. The postmortem blood concentration of
zolazepam was 1.71 I~g/mL. It is very possible that the zolazepam
played a role in enhancing the respiratory depression induced by
the tiletamine and ketamine; however, it is not possible to
describe the extent of that enhancement.
The tremendous difference in the blood concentrations of the
two drugs at first glance appears to be difficult to explain consid-
ering that Telazol is equal parts of tiletamine and zolazepam. The
most likely explanation for the disparity in blood concentrations
of tiletamine and zolazepam would be differences in the distri-
bution, metabolism, and elimination of these two compounds.
The cause of death in this case was ruled an acute mixed drug
intoxication of tiletamine, zolazepam, and ketamine, and the
manner of death was ruled unclassified.
References
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Columns Applications Manual, Revision 691070, Bristol, PA.
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anesthesia in non-human primates. Vet. Med. Small Anita. Clin.
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8. R.C. Baselt and R.H. Cravey. Disposition of Toxic Drugs and
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City, CA, 1995.
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Pharmacokinetics of ketamine in man. Anaesthesia 24:260--263
(1975).
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2H s PCP and selective ion monitoring applied to non-fatal cases of
PCP intoxication. Clin. Chem. 22:1623-1626 (1976).
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Manuscript received March 1, 1999;
revision received May 26, 1999.
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