What Can the Use of Unmetabolizable Lipophilic Compounds Tell About the Importance of Drug Metabolism?

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Abstract
6-CB, a model compound which because of its lipophilicity cannot be excreted by the kidneys and is also unmetabolizable, shows an extreme type of pharmacokinetics. In rats given single doses the compound disappears with a half-life of half a life span by fecal excretion. If adipose tissue mass is allowed to increase, the 75% dose initially stored in adipose tissue does not decrease during 280 days. With repeated weekly administration each dose adds some 90% to the body burden. It is concluded that the old hypothesis of drug-metabolizing enzymes as a protective system preventing accumulation of naturally occurring lipophilic drugs is correct.