The use of a medetomidine,butorphanol and atropine combination to enable blood sampling in young pigs

AIM: To determine the suitability of a reversible, injectable anaesthetic combination including medetomidine, butorphanol and atropine to produce the degree of immobilisation required to allow blood sampling in young pigs.

METHODS: Twenty 6-week-old crossbred, intact male pigs were sedated with an intramuscular (I/M) injection of 80 µ'g/kg medetomidine, 200 µ'g/kg butorphanol and 25 µ'g/kg atropine. Heart and respiratory rates and rectal temperatures were monitored. Excessive salivation, gagging, laryngeal reflex, presence of pedal reflex and deep and surface analgesia were noted. Time of injection and the time when pigs reached mild and full sedation were also recorded.

RESULTS: Mild sedation was produced in 90% of pigs after 5.6 (SEM 0.96) min (n=18; median 5, range 2–16 min), and full sedation (lateral recumbency and loss of jaw tone) in 60% of pigs after 12.5 (SEM 2.14) min (n=12; median 10, range 5-28 min). The depth and duration of sedation were very variable and most animals were easily aroused. Ninety percent of the animals required the administration of halothane by mask to allow blood sampling, but the amount of halothane required was small. Heart and respiratory rates decreased (p<0.001) but remained within the normal range. Rectal temperature was above normal at the time of sedation and at the time of blood sampling when the ambient temperature was 29° C but not when the ambient temperature was reduced to 25°C.

CONCLUSIONS: The combination of medetomidine, butorphanol and atropine at these doses produced sedation of variable depth and duration that was insufficient on its own to allow blood sampling in the majority of pigs. Hyperthermia can occur in temperature-controlled environments when using medetomidine, butorphanol and atropine in pigs. Reduction of stress and a quieter environment may improve the effects of the anaesthetic combination.     

A pharmacokinetic/pharmacodynamic approach vs. a dose titration for the determination of a dosage regimen: the case of nimesulide, a Cox-2 selective nonsteroidal anti-inflammatory drug in the dog

The present experiment was designed to determine a dosage regimen (dose, interval of administration) in the dog for nimesulide, a nonsteroidal anti-inflammatory drug with in vitro selectivity for the inhibition of cyclo-oxygenase 2 (Cox-2), using a pharmacokinetic/pharmacodynamic (PK/PD) approach. The PK/PD results were compared with those obtained using a classical dose titration study. In the PK/PD experiment, 11 dogs were subjected to Freund's adjuvant arthritis characterized by permanent hyperthermia. Nimesulide (5 mg/kg, oral route) was tested during the secondary phase of the inflammatory response. In the dose titration study, nimesulide (0, 3, 6 and 9 mg/kg, oral route) was tested in eight other dogs using a reversible urate crystal arthritis in a 4-period crossover design. Different PD endpoints (including lameness assessed by force plate and hyperthermia) were regularly measured during the PK/PD experiment, and plasma samples were obtained to determine the plasma nimesulide concentration. The data were modeled using an indirect effect model. The IC50 of nimesulide for lameness was 6.26 +/- 3.01 microg/mL, which was significantly higher than the EC50 value obtained for antipyretic effect (2.72 +/- 1.29 microg/mL). The ED50 estimated from the classical dose titration study were 1.34 mg/kg (lameness) and 3.0 mg/kg (skin temperature). The PK/PD parameters were used to simulate different dosage regimens (dose, interval of administration). The antipyretic and anti-inflammatory effects were calculated from the model for the recommended dosage regimen (5 mg/kg/24 h). It was apparent from this approach, that this dosage regimen enabled 76% of the theoretical maximal drug efficacy to be obtained for pyresis and 43% for lameness. It was concluded from the comparison of in vivo and in vitro IC50, that nimesulide is a potent NSAID for which some Cox-1 inhibition is required to obtain clinically relevant efficacy.