Evidence for metabolic inertness of doxycycline

Several conflicting observations in the literature raised considerable doubt about the metabolic fate of doxycycline, which, like other tetracyclines, has been claimed to be metabolically inert. A double liquid chromatographic approach was used in an attempt to demonstrate the polar metabolites and/or conjugates in excreta of human volunteers who ingested the drug. Both ion-exchange and reversed-phase chromatography failed to reveal significant by-products in urine and feces, except for minor amounts of 4-epidoxycycline. In addition, enzymatic hydrolysis procedures did not present any evidence of the conjugates. Thus, the different excretion behavior of doxycycline, compared to other analogs, cannot be explained in terms of increased metabolism.