In a randomized crossover study, five normal subjects were given 250-mg capsules of tetracycline at weekly intervals with cimetidine 300 mg. sodium bicarbonate 2 gm in water, magnesium-aluminum hydroxide gel 30 ml, or water alone. Gastric pH was monitored by radiotelemetry. Antibiotic bioavailability as measured by area under the serum level- time curve, peak serum level, and urinary elimination was not affected by cimetidine or sodium bicarbonate. Magnesium-aluminum hydroxide gel reduced bioavailability by 90%. The data show that gastric pH does not affect absorption of oral tetracycline and that cimetidine can be used in place of antacids to control gastric acid in patients using tetracycline

The effect of oral antacid administration on the pharmacokinetics of intravenous doxycycline was studied. In a randomized crossover design, six healthy male volunteers received an infusion of 200 mg of doxycycline hyclate on two occasions separated by 7 days. On one occasion, subjects were given 30 ml of aluminum hydroxide orally four times a day for 4 days, beginning 2 days prior to doxycycline dosing. Blood and urine samples were collected up to 48 and 96 h after the infusion, respectively, and were analyzed by a microbial assay. Values for volume of distribution at steady state, nonrenal clearance, urine recovery, and urine pH were not statistically different among treatment groups. With concomitant antacid therapy, the half-life of intravenous doxycycline was shortened from 16.2 +/- 2.6 to 11.2 +/- 1.2 h (P = 0.003), and total body clearance increased from 37.4 +/- 6.5 to 54.1 +/- 12.3 ml/min (P = 0.008). Area under the concentration-time curve for serum was decreased by 18 to 44%, with a 22 to 41% increase in renal clearance. Although the increase in nonrenal clearance ranged from 11 to 128%, the high variability led to a nonsignificant difference (P = 0.07). Concomitant oral antacid therapy may significantly enhance the clearance of intravenous doxycycline

Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one- or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillin-clavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P less than 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 +/- 22.7 mg.h/liter, fasting; 6.0 +/- 3.2 mg.h/liter, with antacid), resulting in subtherapeutic levels of doxycycline

9 fors°gspersoner indgÕr i f°lgende behandlingere. A: 250 mg tetracklin aleneB: 250 mg tetracyklin sammen med et standard mÕltid (indeholdende 145 mg calcium)C: 250 mg tetracyklin sammen med mexican mÕltid (indeholdende 235 mg calcium)7 dages wash-out.Unders°gelser viser, at mµngden af tetracyklin i urinen nedsµttes fra 151,2 mg til henholdsvis 90,05 mg (standard mÕltid) og 68,47 mg (mexican mÕltid). Ved pH 7,5 er der 100 % frit tetracyklin, som kan absorberes. Sammen med standard mÕltid er der nogle % tilrÕdighed og sammen med mexican mÕltid er der 0 % tilrÕdighed.

All tetracycline derivatives are bacteriostatics and their concentration in serum should not fall during the therapy below the generally accepted minimum therapeutic concentration of 0.5 to 1.5 mug/ml. Tetracyclines have a high affinity to form chelates with polyvalent metallic cations such as Fe+++, Fe++, Al+++, Mg++ and Ca++. Many of these tetracycline-metal complexes are either insoluble or otherwise poorly absorbable from the gastro-intestinal tract. Milk and other dairy products, antacids containing polyvalent cations, as well as various iron salts ingested simultaneously with tetracycline derivatives, might interfere with their absorption by 50 to 90% or even more. The severity of interaction depends both on the nature of the tetracycline derivative and of the cation, on the doses used, on pharmaceutical factors, and on time schedules in dosing. An interval of 3 hours between the ingestion of tetracyclines and cations prevents the interaction. The pharmacokinetic interactions in absorption of tetracyclines likely to be clinically significant in cases where the infecting pathogens are moderately resistant to tetracyclines and relatively high serum concentrations are needed for proper bacteriostasis

The effect of milk added to coffee or black tea on the bioavailability of tetracycline was evaluated in 12 healthy volunteers according to a crossover design. Results showed that even a small volume of milk containing extremely small amounts of calcium severely impair the absorption of the drug, so that the presence of this metal ion should be carefully controlled in order to avoid decreasing the available tetracycline