Doxycycline carrageenate — an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate

Abstract

The effect of increased gastric pH (obtained by pre-treatment with omeprazole) on the bioavailability of doxycycline monohydrate and doxycycline carrageenate has been investigated in 24 healthy volunteers, using an open, randomised, four-treatment, four-period, crossover, 2×2 factorial design. Each subject received a single dose of 100 mg of each of the doxycycline formulations with and without pre-treatment with omeprazole (40 mg daily for 7 days).

The two formulations were bioequivalent (rate and extent) during fasting without omeprazole pre-treatment, whereas after omeprazole, the monohydrate showed a highly significant decrease in bioavailability (38% for AUC and 45% for C_max) compared to the carrageenate formulation, which was not affected by prior administration of omeprazole. Many of the subjects did not reach a therapeutic plasma level of doxycycline during the combination of omeprazole and doxycycline monohydrate, and most adverse events (mainly gastrointestinal) were reported after this combination.

As large populations of patients have a high gastric pH due to frequent use of H₂-blockers, proton pump inhibitors and antacids, as well as to physiological achlorhydria, the decreased absorption of doxycycline monohydrate may well have a clinical impact, for example when the patients are treated with tetracyclines for an infection.