Serum Concentrations and Behavioral Effects of Oral Haloperidol in Bongo Antelope (Tragelaphus eurycerus)
Neuroleptic drugs have been used to reduce anxiety, excitement, and motor activity in ungulates. These drugs facilitate the handling and transportation of both captive and free-ranging animals. Haloperidol, an antipsychotic, tranquilizing agent, is used in humans to reduce psychomotor agitation and aggression. Parentally administered haloperidol has also been shown to produce desirable psychomotor effects and tractability in a number of ungulate species.2,4 The pharmacologic effects of haloperidol in bongo antelope have not been reported, and further, such effects have not been correlated with plasma concentrations. There is little information on the oral effectiveness of haloperidol in any nondomestic species. The ability to administer an oral tranquilizing agent could obviate the need for repeated administration by remote injection to maintain a desired level of tranquilization.
A dose of 1 mg/kg has been suggested as an oral haloperidol dose.1 Recent clinical observations (S. Mikota, unpublished data) have shown that a 1 mg/kg dose of haloperidol, administered once daily in the food for 5 days, produced a level of tranquilization which permitted restraint and blood sampling without incident in captive bongo conditioned to enter a custom-designed chute. These observations suggested that haloperidol is palatable orally and is absorbed and distributed to the central nervous system. The purpose of this study was to systematically evaluate the behavioral effects of orally administered haloperidol in bongo antelope and to correlate these effects with plasma concentrations.
As part of an ongoing project to evaluate steroid hormones and anti-tuberculosis drug levels, each of four adult female bongo received haloperidol at 4:00 p.m. for 28 days at an approximate dose of 1 mg/kg/day (1.04–1.62 mg/kg). Haloperidol is supplied as 20-mg tablets, and oral dosing was accomplished by inserting 10 tablets into bananas which were hand fed to individual animals by a keeper who had established the animals’ trust.
A push wall directed bongo to enter a chute and squeeze box. Bongo were blindfolded upon entering the chute and two straps placed dorsally across the back to discourage jumping. Venipuncture sites were shaved with a disposable razor and a 4% tetracaine ointment applied. (Application of tetracaine alone did not result in analgesia sufficient for blood sampling.; S. Mikota, unpublished data). Blood samples to measure plasma progesterone and estradiol were collected daily for 29 days.
On day 20, blood was drawn at 6:30 a.m. (time 0); haloperidol was administered orally as described; and anti-tuberculosis drugs were administered orally and/or parentally. Bongo were bled at 1, 2, 3, 5, 8, 10 and 12 hours post-administration to measure serum concentrations of anti-tuberculosis drugs and haloperidol over time.
Bongo were observed under four sets of conditions as follows:
- Condition 1: Confined to pen; on haloperidol
- Condition 2: Manipulation through chute; venipuncture; on haloperidol
- Condition 3: Manipulation through chute; venipuncture; not on haloperidol
- Condition 4: Manipulation through chute; venipuncture; on haloperidol (4-day study)
Score cards, devised to subjectively grade the degree of tranquilization observed under conditions 1–4, were completed by all personnel involved in the procedure. Parameters included behavior in pen, behavior in chute, appetite, and response to treats. Pen and chute behaviors were scored using a 7-point subjective scale that described the animal’s behavior in each setting. The behavioral scores ranged from unresponsive to violent. Overall behavior was scored using a 4-point scale that described general impressions of the performance of the tranquilizer. These scores ranged from unacceptable to excellent. Temperature, pulse, and respiration were measured at each time point and animals were observed for possible side effects (repetitive muscle jerks [dystonia], drooling, worm-like movements of the tongue [lingular vermiculation], spontaneous rolling back of the eyes [oculogyric crisis] or slow, repetitive, purposeless movements [tardive dyskinesia]). Behavioral data from all observers was averaged and a single score generated for each animal and variable.
Condition 4 behavioral data was collected for 4 consecutive days following 13 days during which bongo did not receive haloperidol.
Serum haloperidol was measured using a commercially available enzyme-linked immunosorbent assay (ELISA) in a 96-well microtiter plate format. The assay was validated for bongo serum using samples from untreated animals and fortification of the samples with haloperidol reference standard. Samples were assayed in singlicate against blanks and blank fortified reference standard controls.
At time 0, 14.5 hours since the last haloperidol dosing, mean serum concentration of haloperidol was 12.6 ng/ml and overall behavior was scored as fair to good (1.7). Over the next 1–3 hours, the steepest increases in haloperidol concentration and overall behavior score were observed. At 2 hours post-dose, overall behavior was scored as good to excellent (2.7), and serum haloperidol concentrations had risen to 16.2 ng/ml. While serum concentrations continued to rise for 10 hours post dose, increases became more gradual from 3–10 hours, reaching a peak at 10 hours (19.5 ng/ml). Overall behavioral scores remained fairly constant (from good to excellent) from 3–10 hours post. During this time, the animals could be easily approached and did not attempt to escape the chute. They readily tolerated venipuncture, blindfolding, restraint with dorsally placed straps, stethoscopic auscultation, and the insertion of a digital thermometer. The bongo also complied with physical coaxing towards the chute and ambulated normally upon leaving the chute. Little or no change in chute or overall behavior was reported during that time. Although behavior was not scored, serum haloperidol concentration began to decline (17.3 ng/ml) by 12 hours post dose.
General appetite, as measured by treat consumption, increased from partial consumption at time 0 to complete consumption by 3 hours post dose. Consumption remained complete for the remaining observation period. Respiratory rate, body temperature, and ambient temperature rose gradually during the 10-hour observation period. Pulse rate was variable.
The data obtained from conditions 1–3 indicated that adequate plasma concentrations of haloperidol could be achieved in bongos via the oral route of administration. Furthermore, the data indicated that serum concentrations could be correlated with changes in behavior. The most dramatic improvements in tranquilization were seen during the most rapid increases in serum concentrations (i.e., 1–3 hours post dose). The data also demonstrated that plasma haloperidol concentrations appear to peak at 10 hours post dose and that good to excellent tranquilization could be achieved at 15–19 ng/ml.
Residual haloperidol concentrations of 8.38–8.5 ng/ml were measured at 24 hours post dose, suggesting that haloperidol is absorbed gradually and reliably from the gastrointestinal tract, even in the presence of food. Plasma concentrations of 5–15 ng/ml have been associated with positive therapeutic responses in humans.3 Similar plasma concentrations were achieved in our study, suggesting that the therapeutic range for humans and bongos is similar. In conclusion, a once-daily oral dose (200 mg) of haloperidol produced a desirable level of tranquilization in bongos that permitted manipulation and blood sampling.
This project was funded in part by grants from the Institute of Museum and Library Services, the Conservation Endowment Fund of the American Zoo and Aquarium Association and Ortho-McNeil. A special “thank you” is extended to the hoofstock staff at the Audubon Park Zoo for their dedicated effort to make this project possible.
1. Blumer ES. 1991. A review of the use of selected neuroleptic drugs in the management of nondomestic hoofstock. Proc. Am. Assoc. Zoo Vet. Calgary: 33–339.
2. Gandini GCM, Ebedes H, Burroughs REJ. 1989. The use of long-acting neuroleptics in impala. (Aepyceros melampus). S. Afr. Vet. Ver. 60(4):206–207.
3. Forsman A, Ohmann R. 1974. Applied pharmacokinetics of haloperidol in man. Current Ther Res. 20:1255–1270.
4. Hofmeyr, J.M. 1981. The use of haloperidol as a long-acting neuroleptic in game capture operations. J. S. Afr. Vet. Assoc. 52(4):273–282.