What can the use of unmetabolizable lipophilic compounds tell about the importance of drug metabolism?

Drug Metabolism Reviews
M H Bickel

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.

References

May 1, 1980·Toxicology and Applied Pharmacology·H B Matthews, D B Tuey
May 1, 1980·Toxicology and Applied Pharmacology·S KatoH B Matthews
Jan 1, 1980·Drug Metabolism Reviews·M H Bickel, S Muehlebach
Apr 1, 1981·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S Mühlebach, M H Bickel

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Citations

May 27, 2008·International Archives of Medicine·Shanmugam SivabalanVenugopal P Menon

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