Binding of narcotic analgesics to plasma and tissues in vitro

Binding of ³H-fentanyl, ¹⁴C-methadone and ³H-l-α-acetyl-methadol (³H-LAAM) to rat plasma and tissues was studied in vitro. Tissue homogenates of brain, lung, heart, liver, kidney and skeletal muscle (10% w/v) were dialysed, at 24°C, against 1.0 μm of each radiolabeled compound in Krebs-Ringer phosphate buffer for 5 hr to reach equilibria. ³H-LAAM was bound more extensively (28-62%) to plasma and tissue homogenates than ¹⁴C-methadone (16-57%) which, in turn, was bound more than ³H-fentanyl (16-37%). Liver had the highest affinity for all three drugs whereas muscle and plasma appeared to have the lowest. Other tissues generally had a lower affinity for the three drugs. There was no apparent relationship between the percent of drug bound and the total protein concentration in each tissue. However, for each drug there was a good correlation between the percent drug bound and its octanol/water partition coefficient. The differences in the duration of action between fentanyl, methadone and LAAM may be explained by the differences in their plasma and tissue binding.