Abstract
1. 1. The effect of experimental inflammation on methadone analgesia was evaluated in rats, by the tail-flick test, after single intravenous (0.35 mg/kg) and subcutaneous (3 mg/kg) doses. 2. 2. After i.v. administration a significant decrease ( P < 0.05) in the area under the methadone time-response curve was seen in rats with experimental inflammation, when compared with control. However, no differences in the analgesic response to methadone were detected between control rats and rats with inflammation when the drug was administered by s.c. injection. 3. 3. Plasma mucoprotein levels were significantly increased ( P < 0.001) and methadone free fraction was significantly decreased in rats with inflammation ( P < 0.05). In addition, after i.v. methadone a decrease in brain uptake in rats with inflammation was detected. A significant correlation between brain uptake index and plasma free fraction was also observed. 4. 4. These results suggest that a decreased immediate response to i.v. methadone may occur in circumstances in which there is an increase in α 1 acid glycoprotein, but that this is not likely to be observed when the absorption is not instantaneous.
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