title: Beyond-use dating of extemporaneously compounded ketamine, acepromazine, and xylazine: safety, stability, and efficacy over time.
abstract: Ketamine-acepromazine-xylazine (KAX) has long been a popular combination of injectable anesthetics for use in laboratory rodents. These drugs are compounded extemporaneously at research facilities because a commercial mixture is not available. This study was designed to determine an appropriate period of use for this mixture by examining its safety, stability, and efficacy at 30-d intervals over an aging period of 270 d. For as long as 270 d after compounding, most of the data collected (chemical stability, sterility, pH, particulate formation, times to loss of righting reflex in injected mice and rats, and histopathology from these animals) supported the finding that the component drugs do not change or degrade. However, mice and rats did show significant differences in anesthetic responses after injection with KAX mixtures of different ages. In light of these findings, we suggest that KAX remains safe, stable, and efficacious for at least 180 d after mixing, and that 180 d constitutes an appropriate period of use for this drug combination when stored in a dark, room-temperature environment.
authors.affiliation: The United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. brett.taylor@us.army.mil
authors.forename: Brett J
authors.initials: BJ
authors.lastname: Taylor
authors.forename: Steven A
authors.initials: SA
authors.lastname: Orr
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Chapman
authors.forename: Diana E
authors.initials: DE
authors.lastname: Fisher
mesh_terms: D000075:Acepromazine / Q000032:analysis / Q000494:pharmacology*; D000758:Anesthesia; D019162:Anesthetics, Combined / Q000032:analysis / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007649:Ketamine / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009949:Orientation / Q000187:drug effects; D010147:Pain Measurement; D051381:Rats; D011914:Rats, Inbred BN; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D014991:Xylazine / Q000032:analysis / Q000494:pharmacology*
chemical_list: D019162:Anesthetics, Combined; D014991:Xylazine; D000075:Acepromazine; D007649:Ketamine