Adipose tissue storage of drugs as a function of binding competition. In-vitro studies with distribution dialysis.
Distribution dialysis was used to study binding competition between homogenates of adipose tissue and of lean tissues. The concentration ratios adipose/X (X = blood, muscle, lung, liver) of eight lipophilic drugs were determined in the absence and in the presence of a competing binding system X. With drugs which do not undergo storage in adipose tissue in-vivo, yet have a high volume of distribution, such as imipramine or desipramine, there was strong binding competition, and the balance of distribution was shifted from adipose to lean tissues. In the case of indomethacin with a low volume of distribution this shift was from adipose tissue to blood. With diazepam there was a marked binding competition which was not, however, sufficient to shift the balance of distribution away from adipose tissue. Binding competition was negligible with thiopentone. In contrast, with the equally lipophilic hexethal a moderate binding competition was observed. This is consistent with a decreased adipose tissue storage of the latter barbiturate. It is concluded that binding competition exists not only between blood and tissues but also among individual tissues. It is suggested that occurrence and extent of adipose tissue storage of drugs are determined by binding competition between lean and adipose tissues and, more generally, that distribution of lipophilic drugs is largely a function of binding competition.
Minder
S
S
Department of Pharmacology, University of Berne, Switzerland.
Daniel
W A
WA
Clausen
J
J
Bickel
M H
MH
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics*; D001569:Benzodiazepines; D001667:Binding, Competitive; D001769:Blood / Q000378:metabolism; D003956:Dialysis; D007213:Indomethacin / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D010653:Phenylbutazone / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D010653:Phenylbutazone; D007213:Indomethacin