Differences in adipose tissue distribution of basic lipophilic drugs between intraperitoneal and other routes of administration.

1. Distribution of 14C-methadone in male rats was studied after administration of single i.p. doses. Highest concentrations were attained after 30 min in the decreasing order of abdominal adipose tissues, liver, lung, other organs. Concentrations in abdominal adipose tissues were 20 times higher than in subcutaneous adipose tissue. This is in contrast with what occurs with other routes of administrations, where only low concentrations are attained in both subcutaneous and abdominal adipose tissues. 2. The situation in the peritoneal cavity after i.p. injection was simulated in vitro by incubation of whole, excised abdominal adipose tissues of rats with methadone and other basic drugs (dibenzepine, alprenolol, opipramol, propranolol, chlorpheniramine, desipramine, imipramine and chlorpromazine) for 6 h at pH 7.4. These drugs were readily taken up (25 to 74% at equilibrium). 3. There was a positive correlation between uptake and lipophilicity of the drugs as measured by log P (octanol/water). Less lipophilic drugs such as amphetamine, morphine and chlorphentermine were not appreciably taken up from the incubation medium. The threshold log P-value for appreciable adipose tissue uptake is around 2. 4. It is concluded from these data and related studies that basic lipophilic drugs are not stored in adipose tissues in vivo, except when given via the i.p. route. In the latter case the storage appears to result from non-systemic, diffusional uptake from the peritoneal cavity.