Metadon till hund : klinisk farmakologi
Abstract: Methadone is frequently used as an analgesic drug for dogs although there are very few studies describing the pharmacokinetics of methadone in this species. In man methadone has a long half-life and there are considerable differences in pharmacokinetics between individuals. The dose interval is lengthened when the drug is used fore longer periods of time due to prolonged half-life. Therefore the drug dose must be adjusted individually. The purpose of this study was to study the fundamental pharmacokinetics of methadone in dogs, and to find an optimal drug dosage. We also measured parameters that are used in pain evaluation because it would be valuable in evaluating the clinical effects of methadone. These parameters were blood plasma concentrations of the hormones vasopressin and cortisol and behavioral studies. Ten clinically healthy Beagles and Beagle crosses were used. Five were males and five females. The design was a crossover study. Five dogs got 0.4 mg/kg of methadone IV and five got 0.4 mg/kg SC after which a three week washout period followed. Due to a misunderstanding, only four dogs then got the drug IV while six dogs got the same dose SC. Plasma concentrations of methadone were analyzed and after IV administration half-life was 3,9 h ± 1,0 h (average ± SD). The half-life after SC administration was longer and varied more, it was 10,7 h ± 4,3 h. (average ±SD). The behavioral study started 40 min after drug administration. The behavior of each dog was also studied on a control day when the dog did not receive methadone. The behavioral study showed that the dogs lied down more after the methadone injection. The dogs whined four and a half times more after methadone injection than during control days. The dogs showed less of the behaviors muscle tremor, snout licking and swallowing. This latter change of behavior was related to lower blood plasma cortisol concentrations after SC administration at 30 min and at 3,6 and 30 hours compared to before methadone injection. In contrast, the cortisol levels were elevated after IV injection at 1 h presumably as a result of drug induced systemic release. However, the changes in behavior were similar after IV and after SC administration. A drug induced rise of the vasopressin levels were recorded at 30 min after IV injection, which is in agreement with a previous study of methadone in dogs. In conclusion, SC administration is to prefer before IV, because of the longer half life that enables longer dose intervals. However, large individual differences in pharmacokinetics were observed after SC administration, which complicates the use of the drug. Methadone has got a sedating effect, reduces stress and dose not induce sickness. We also conclude that plasma concentrations of cortisol and vasopressin increased in relation to the concentration of methadone and are therefore not useful parameters in evaluating pain when methadone has been given. In addition, whining is not a reliable parameter in pain evaluation, because of its increase after methadone administration.
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