E. Gomez et al., ALTERED METHADONE ANALGESIA DUE TO CHANGES IN PLASMA-PROTEIN BINDING - ROLE OF THE ROUTE OF ADMINISTRATION, General pharmacology, 26(6), 1995, pp. 1273-1276
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. After i.v. administrat
ion a significant decrease (P <0.05) in the area under the methadone t
ime-response curve was seen in rats with experimental inflammation, wh
en compared with control. However, no differences in the analgesic res
ponse to methadone were detected between control rats and rats with in
flammation when the drug was administered by s.c. injection. 3. Plasma
mucoprotein levels were significantly increased (P <0.001) and methad
one free fraction was significantly decreased in rats with inflammatio
n (P <0.05). In addition, after i.v. methadone a decrease in brain upt
ake in rats with inflammation was detected. A significant correlation
between brain uptake index and plasma free fraction was also observed.
4. These results suggest that a decreased immediate response to i.v.
methadone may occur in circumstances in which there is an increase in
alpha(1) acid glycoprotein, but that this is not likely to be observed
when the absorption is not instantaneous.