Doxycycline carrageenate--an improved formulation providing more reliable absorption and plasma concentrations at high gastric pH than doxycycline monohydrate.
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, cross-over, 2 x 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 Cmax) 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.
Pharmaco Medical Consultants-PMC AB, Uppsala, Sweden.
A
A
Grahnén
B
B
Olsson
G
G
Johansson
S A
SA
Eckernäs
D000328:Adult; D000704:Analysis of Variance; D001682:Biological Availability; D002351:Carrageenan / Q000097:blood / Q000493:pharmacokinetics*; D004318:Doxycycline / Q000097:blood / Q000493:pharmacokinetics*; D004338:Drug Combinations; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007408:Intestinal Absorption; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D014677:Pharmaceutical Vehicles; D013270:Stomach / Q000187:drug effects
D004338:Drug Combinations; D014677:Pharmaceutical Vehicles; C093434:doxycycline carrageenate; D002351:Carrageenan; D009853:Omeprazole; D004318:Doxycycline