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 ho mogenates of adipose tissue and of lean tissues. The concentration rat ios adipose/X (X=blood, muscle, lung, liver) of eight lipophilic drugs were determined in the absence and in the presence of a competing bin ding system X. With drugs which do not undergo storage in adipose tiss ue 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 com petition which was not, however, sufficient to shift the balance of di stribution away from adipose tissue. Binding competition was negligibl e 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 con cluded that binding competition exists not only between blood and tiss ues but also among individual tissues. It is suggested that occurrence and extent of adipose tissue storage of drugs are determined by bindi ng competition between lean and adipose tissues and, more generally, t hat distribution of lipophilic drugs is largely a function of binding competition.