Methadone-induced respiratory depression in the dog: comparison of steady-state and rebreathing techniques and correlation with serum drug concentration.

The respiratory effect of di-methadone administered subcutaneously was examined in awake, unsedated female Labrador retrievers in which a chronic tracheostomy had been established. Respiratory depression was determined from the change in ventilatory response to carbon dioxide. Two methods for assessing the response were evaluated and compared, namely the classical steady-state and rebreathing techniques. Maximal methadone-induced respiratory depression after administration of 2 mg/kg of dl-methadone occurred by 1 hr as detected by both methods, but the magnitude of the response as detected by the steady-state technique was significantly greater. At 8 hr significant respiratory depression was still detectable by the steady-state but not by the rebreathing technique. At comparable serum drug levels, the rebreathing method consistently detected a smaller degree of drug-induced respiratory depression. Methadone administration produced a decrease in slope of the ventilation-response curve which was significant at 1 and 2 hr for both methods. Slopes of the response curves obtained at pretreatment control measurements were markedly different for the two techniques, being significantly greater for the rebreathing method. Serum dl-methadone concentration was measured by radioimmunoassay. The mean serum half-life of methadone was 4.7 hr. There was excellent correlation between the logarithm of serum drug concentration and drug-induced respiratory depression as measured by either technique.