Pharmacokinetics of epidural butorphanol in isoflurane‐anaesthetized dogs

Abstract

Sixteen healthy male dogs were used at random in this protocol. The dogs were anaesthetized with isoflurane in oxygen. Eight of the dogs received 0.25 mg/kg of butorphanol (group B) and the others an equal volume of isotonic saline (group S) administered by a catheter inserted in the lumbosacral epidural space. Butorphanol concentrations in plasma and cerebrospinal fluid (CSF) were measured using high-performance liquid chromatography with electrochemical detection. Maximum concentration of butorphanol and time to obtain this concentration were 42.28 ng/mL at 13.88 min in blood, and 18.03 ng/mL at 30 min in CSF. Volume of distribution, clearance, mean distribution and elimination half-lives were respectively 4.39 L/kg, 2.02 L/h.kg, 16.5 min and 189.1 min. Mean isoflurane minimal alveolar concentration values for group B obtained following hind- or forelimb stimulation decreased by 31% after epidural butorphanol. Cutaneous analgesia (to pin-prick test) persisted for 3 h after the end of isoflurane anaesthesia in group B and was in correlation with the plasmatic analgesic dose of butorphanol (9 ng/mL). These results suggested that analgesia was predominantly obtained by action of butorphanol on the supraspinal structures following its vascular systemic absorption.

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration

“…25 In cats, somatic analgesia is induced only with a high dose of butorphanol (0.8 mg/kg [0.36 mg/lb]), compared with visceral analgesia, which is apparent after lower doses (0.1 mg/kg, IV, and 0.4 mg/kg [0.18 mg/lb], SC). These concentrations are similar to the targeted plasma butorphanol concentration for somatic analgesia (response to pin prick) in dogs at 9 to 10 ng/ml 26 and to the targeted plasma concentration for visceral analgesia in horses (20 to 30 ng/ml). Although visceral analgesia was not tested in this study, plasma concentrations > 9.2 ng/ml and possibly as high as 21.0 to 23.8 ng/ml were associated with somatic analgesia in the llamas.…”

Pharmacokinetics and Intramuscular Bioavailability of a Single Dose of Butorphanol in Asian Elephants (Elephas maximus)

“…41 The lower mean C max concentration compared with the therapeutic concentrations of horses (20 ng/ml), goats (9 ng/ml), llamas (>9.2 ng/ml), dogs (9 ng/ml), and cats (45 ng/ml) with clinically subjective therapeutic effect indicates that elephants may be very sensitive to this opioid. 6,7,41,44,47 This sensitivity could be due to the concentration at the receptor sites or differences in the distribution of these sites. Analgesia is determined by the concentration at the receptor site, which does not necessarily correlate with the plasma concentration.…”

“…The pharmacokinetic parameters of V dss and Cl p used to compare predicted elephant values with those determined in this study were obtained from the published literature for rabbit, dog, human, cattle, goats, horses, and llamas. 6,7,9,37,41,42,44 …”

Avaliação algimétrica por estímulo nociceptivo térmico e pressórico em cães pré-tratados com levomepromazina, midazolam e quetamina associados ou não ao butorfanol ou buprenorfina

“…Um efeito-teto similar também ocorre para a analgesia. O butorfanol é eficaz como suplemento durante anestesia balanceada e causa menor depressão respiratória pós-operatória que a morfina 10 . Da mesma maneira que o butorfanol pode ser asssociado em anestesia injetável balanceada 10 , a buprenorfina é também uma alternativa para melhorar a qualidade desta modalidade anestésica 11 .…”

“…O butorfanol é eficaz como suplemento durante anestesia balanceada e causa menor depressão respiratória pós-operatória que a morfina 10 . Da mesma maneira que o butorfanol pode ser asssociado em anestesia injetável balanceada 10 , a buprenorfina é também uma alternativa para melhorar a qualidade desta modalidade anestésica 11 . A buprenorfina foi descrita como sendo um derivado semi-sintético da tebaína; é um analgésico potente e pode ser administrado pela via intravenosa ou intramuscular, obtendo-se um efeito total lento após administração intravenosa, entretanto uma vez estabelecida a analgesia é mantida por um período prolongado 11 .…”