Doxycycline is not listed as an inducer or as a mechanism–based inhibitor of any CYP enzymes. It is mainly excreted unchanged in urine and faeces. CYP enzymes are most probably only involved in the metabolism to a minor extent. Side effects such as nausea, vomiting and diarrhoea may be potentially porphyrinogenic through reduction in carbohydrate intake.

Doxycycline is a tetracycline broadspectrum antibiotic with alkylamino group. It is 3-5 times more lipophilic than tetracycline (Agwuh 2006, Whelton 1974).

It is used in the treatment of infections caused by tetracycline sensitive aerobe and anaerobe Gram-positive and Gram-negative microorganisms. Nausea, vomiting and diarrhoea are reported as very common side effects.

Significant.

In vitro studies suggests that doxycycline might be a substrate or an inhibitor of CYP3A4 (Eisen 2010, Zhao 1997, 1999) but no data indicates mechanism-based inhibition. It is highly protein bound (90%) and diffuses from blood into the intestinal lumen, where cationic chelation occurs. This prevents reabsorption (Whelton 1974) and it is then excreted in faeces. The remainder (30-60%) of administered doxycycline is normally excreted unchanged in urine (Agwuh 2006, Houin 1983, SPC). Half-life elimination: single dose 16-18 hours, following multiple doses: 22 hours. In vivo studies have shown that the half-life of doxycycline shortens when administered with phenobarbital, an inducer of CYP enzymes (Nuevonen 1974). Rifampicin, an inducer of CYP enzymes as well (Kolars 1992) has also been shown to lower the levels of doxycycline in plasma when co-administered (Colmenero 1994). These data indicates that doxycycline might be a substrate of CYP enzymes and that CYP enzymes may be involved in its metabolism to some extent. There are no reports of doxycycline as a perpetrator in drug-drug-interactions concerning CYP enzymes.

S. Thunell: 2 reports of safe use.

One report of uneventful use of doxycycline in female AIP patient (7 days). Urinary porphyrin concentrations was measured before and after treatment, and doxycycline was considered entirely safe (Smith JR 1989).

Uneventful use reported in 9 patients with acute porphyria.