Xylazine Veterinary Use
xylazine hcl is a non-narcotic compound that is commonly used as a sedative and analgesic, as well as a muscle relaxant. Xylazine has a long-standing use for surgical procedures in small animal practices, but it is also used in large animal and wildlife applications. In veterinary anesthesia, xylazine has often been used in combination with ketamine.
The sedative and analgesic activity of xylazine is related to central nervous system depression. It provides muscle relaxation based on inhibition of the intraneural transmission of impulses in the central nervous system.1 The degree of CNS inhibition is such that xylazine provides dose-dependent, deep muscle relaxation and respiratory depression without inhibition of the nervous system’s more critical functions.
In terms of general pharmacology:
A sleeplike state, the depth of which is dose-dependent, is usually maintained for 1 to 2 hours, while analgesia lasts from 15 to 30 minutes. The centrally-acting muscle relaxant effect causes relaxation of the skeletal musculature, complementing sedation and analgesia.
In horses and Cervidae under the influence of xylazine, the respiratory rate is reduced as in natural sleep. Following treatment with xylazine, the heart rate is decreased and a transient change in the conductivity of the cardiac muscle may occur, as evidenced by a partial atrioventricular block. This resembles the atrioventricular block often observed in normal horses.2
As a horse tranquilizer, xylazine HCl is offered in injectable forms, usually supplied in 50 ml multiple dose vials or 100 ml multiple dose vials. To accommodate both small and large animal applications, xylazine is available in a variety of concentrations. pH is normally adjusted using citric acid and sodium (sodium citrate or sodium citrate dehydrate).
Comparative pharmacokinetics of xylazine in several species was reported by researchers in 1981. Xylazine drug was administered intravenously and intramuscularly at recommended doses. The data was generated by analyzing serum drug concentration in samples obtained at 1, 2, 4, 8, 16, 30 and 120 min after xylazine administration. Compartmental analysis of the data was performed and the data best fitted a two-compartment open model.3
Table 1. Major pharmacokinetic parameters of xylazine in horse, cattle, sheep and dog after intravenous administration at 0.6, 0.2, 1.0 and 1.4 mg/kg, respectively
Parameter
Horse (n = 4)
Cattle (n = 4)
Sheep (n = 6)
Dog (n = 4)
Weight (kg)
415-550
240-440
42-65
14-24
t1/2 (min)
50
36
25
30
CLb (ml/min/kg)
21
42
83
81
Vd(area) (l/kg)
2.4
1.9
2.7
2.5
The terminal half-life of xylazine in all species was short indicating that xylazine concentration would decrease to undetectable level within a few hours. The total body clearance varied significantly and was fastest in sheep and dog and slowest in horse. Xylazine clearance has been attributed mainly to metabolic clearance. Therefore, there seems to be species variations in the metabolic rate of the drug. The volume of distribution was large in all species apparently because of the lipophilic nature of the compound.3
The pharmacokinetic parameters after IM administration are given in Table 2. There were no differences in the half-lives after IM administration when compared to those after IV administration. The Tmax values were reached within 15 minutes from drug administration and the peak concentrations were very low. Because of the low concentrations of the drug in bovine plasma, pharmacokinetic parameters after IM administration could not be determined in cattle.3
Table 2. Majorpharmacokinetic parameters of xylazine in horse, cattle, sheep and dog after intramuscular administration at 0.6, 0.2, 1.0 and 1.4 mg/kg, respectively
Parameter
Horse (n = 4)
Cattle (n = 4)
Sheep (n = 6)
Dog (n = 4)
Weight (kg)
415-550
240-440
42-65
14-24
t1/2 (min)
58
N.D.
22
35
Tmax (min)
13
N.D.
15
13
C(max) (m g/ml)
0.2
N.D.
0.1
0.4
Two studies using radiolabelled xylazine were performed by researchers in 1975 and 1978. One study in which 4 animals (two steer calves, one bull calf and a dairy cow) were given xylazine intramuscularly utilized 14C-label in the 4'-position of the thiazine ring of the compound. The other study was conducted on 5 animals, two steer calves, one bull calf and two dairy cows, and were administered xylazine intramuscularly that carried a 14C-label in 4-position of the aniline ring of the molecule. In both studies a dose of 0.33 mg/kg was used.4
In both studies, recovery of radioactivity from urine and feces increased as a function of time (Tables 3 and 4). At 10 hours after administration of the two differently labeled compounds 51-68 % of the radioactivity was recovered. Between 24-72 hours post administration 83-100% of the radiolabel was recovered except for one bull calf where a recovery of only 38% was recorded at 72 hours following administration.4
Table 3. Recovery of radioactivity in urine and feces of 4 animals (cattle) treated intramuscularly with xylazine at 0.33 mg/kg carrying 14C-label in the 4'-position of the thiazine ring of the compound.
Animal
Steer calf
Steer calf
Bull calf
Dairy cow
Time after administration (h)
10
24
48
74
% radioactivity recovered
Urine
65
71
63
77
Faeces
3
15
20
23
Total
68
86
83
100
Table 4. Recovery of radioactivity in urine and feces of 4 animals (cattle) treated intramuscularly with xylazine at 0.33 mg/kg carrying 14C-label in the 4-position of the aniline ring of the compound.
Animal
Steer calf
Steer calf
Bull calf
Dairy cow
Dairy cow
Time after administration (h)
10
48
72
72
72
% radioactivity recovered
Urine
48
82
35
73
85
Faeces
3
15
3
10
14
Total
51
97
38
83
99
After administration of xylazine 14C-labelled in the 4'-position of the thiazine ring at 0.33 mg/kg, radioactivity equivalent to 0.004 mg xylazine/kg or higher was found in all the 12 different analyzed tissues collected from the treated animals. Highest concentrations were measured in the injection site, kidney and liver (0.022-0.406 mg/kg). When xylazine was administered as above but with a 14C-label in the 4-position of the aniline ring, radioactivity exceeding the detection limit was found in all injection site, kidney and liver samples (0.009-1.152 mg/kg), and in all samples collected from the steer calf sacrificed 10 hours after drug administration (0.009-0.761 mg/kg). The characteristics of these residues were not studied and due to the difference in sensitivity of the radiolabel detection in the two studies it was difficult to predict whether the residues consist of double or single ring structures.4
Several other tissue residue depletion studies were conducted between 1969 and 1991. The first of these studies showed that the injection site residues declined to less 1/1000 in 20 hours after xylazine administration at 1.0 mg/kg to sheep. In the same study peripheral muscle concentrations were between 0.09 and 0.21 mg/kg during the same period. None of the other studies were able to detect xylazine residues in tissues when detection level was 0.01 mg/kg an muscle and 0.05 mg/kg in liver and kidney tissues. These studies were conducted in bovine after single IM dose of 0.3 mg/kg. It should be emphasized that the analytical procedures used in the different studies were essentially different and apparently contributed significantly to the discrepancies between the studies.6,7
Detectable radioactivity in milk was found up to 72 hours after administration of the 14C-xylazine labeled in the 4'-position of the thiazine ring and up to 24 hours after administration of the 14C-xylazine labeled in the 4-position of the aniline ring. The chemical nature of these residues was not investigated.5
Xylazine residues in bovine milk were investigated in studies conducted in 1990 and 1991. A single IM dose of 0.3 mg/kg was used. In the first study xylazine concentrations exceeding the 0.01 ppm detection level were not observed when milk samples were collected after each milking for 7 days. In the second study, in 3 samples out of 6, concentrations ranging from 0.012 to 0.019 were detected 5-8 hours after xylazine administration at 0.3 mg/kg IM to lactating cows.5,7
In an earlier study, xylazine milk concentrations in 2 cows after IM administration at 0.2 mg/kg were determined. In this study concentrations ranging from 0.03 to 0.08 m g/ml were found at 5 and 21 hour after administration.5
For veterinary sedation, the available literature recommends
Dogs and cats: 0.25 to 0.5 mg per pound (0.5 to 1 mg/kg) intravenous or 0.5 to 1 mg per pound (1 to 2 mg/kg), intramuscular or subcutaneous.
Xylazine for horses and Cervidae: Intravenous - 0.5 ml/100 lbs body weight (0.5 mg/lb); Intramuscular - 1.0 ml/100 lbs body weight (1.0 mg/lb)
Following administration of xylazine, animals should be allowed to rest quietly until the full effect of the medication has been reached.
The illicit use of xylazine among injecting drug users (IDUs) on the island of Puerto Rico (a territory of the United States) has drawn significant attention for its unprecedented scale and depth. Although Puerto Rican IDUs have reported using this drug since the early 2000s, little has been done in the research and service delivery sectors despite the fact that xylazine severely impacts the health of these illicit users.
Data from one semi-structured interview collected in New York City (2007-2008) as part of a larger research study with migrant Puerto Rican drug users was presented in one case study. Among these users, xylazine has been used as an adulterant and complement to other drugs; its chronic use is reported to be associated with the acceleration of addicts’ physical deterioration.
Clinical findings reported that xylazine users presented limb skin lesions, ulcerations and greater physiological deterioration than heroin users only. One study demonstrated that xylazine inhibits endothelial cell proliferation at lower concentrations than cocaine and heroin. These findings support that xylazine use increases the toxicity of cocaine and heroin when used in combination and induces cell death by apoptosis.8
Because human xylazine use has been reported in other locations outside of Puerto Rico, this substance could also emerge as an adulterant in other markets to the levels currently experienced in Puerto Rico. Researchers believe that interventions will be needed to provide better understanding of how the use of xylazine affects its users, and to reduce the possibility of increased xylazine use in the continental United States.
Xylazine 333 mg/ml by NexGen provides superior relaxation and recovery times when used in veterinary anesthesia applications.
Side effects of xylazine can include muscle tremors, seizures or slowed heart rate with partial heart block and slowed breathing rate. Increased urination sometimes occurs in cats. Dogs can swallow excess air and can bloat under the effects of xylazine, with stomach tubing being necessary to remove excess air in the stomach. Vomiting can occur following xylazine administration in dogs and cats.2
Xylazine is available in the U.S. through numerous pharmaceutical manufacturers and through veterinary custom compounding companies.
FOR RX ONLY: A valid prescription from a licensed veterinarian is required for dispensing this medication.
1Khursheed R., et. al. Evaluation of xylazine and ketamine for total intravenous anesthesia in horses, American Journal of Veterinary Research 2005 66:6, 1002-1007.
2drugs.com.
3Garcia-Villar, R., Toutain, P-L., Alvinerie, M. and Ruckebusch, Y., (1981). The pharmacokinetics of xylazine hydrochloride: An interspecific study. J. Vet. Pharmacol. Therap. 4, 87-92.
4Heukamp, U., (1991a). Tissue concentrations of xylazine in calves following intramuscular administration of Rompun - analytical phase. Bayer Study Report BAY 160.
5Heukamp, U., (1991b). Milk concentrations of xylazine in dairy cows following intramuscular administration of Rompun - analytical phase. Bayer Study Report BAY 161.
6Mutlib, A., Chui, Y., Young, L. and Abbott, F., (1992). Characterization of metabolites of xylazine produced in vivo and in vitro by LC/MS/MS and GC/MS. Drug Metab. Dispos. 20, 840-848.
7Murphy, J. and Jacobs, K., (1975). Residues of Rompun and its metabolites in cattle. Bayer Study Report No. 43814, Bayer AG. Leverkusen, Germany.
8Torruella, R.A. Xylazine (veterinary sedative) use in Puerto Rico. Subst Abuse Treat Prev Policy 6, 7 (2011). https://doi.org/10.1186/1747-597X-6-7
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