Effect of Food or Milk
The effect of food or milk on GI absorption of doxycycline appears to be variable, and further study is needed to clarify whether this variability depends on the specific salt (doxycycline calcium, doxycycline hyclate, doxycycline monohydrate) or dosage form (conventional capsules, tablets, or oral suspension; extended-release capsules or tablets) and/or the food parameters (food with or without milk, high- or low-fat meal, whole or skim milk). There is evidence that administration with food or milk can decrease the rate and extent of absorption of oral doxycycline; however, a slight increase in the extent of absorption also has been reported in some individuals who received the drug with food. Although a few manufacturers and clinicians suggest that the effect of simultaneous ingestion of food or milk is not likely to be clinically important and doxycycline may be administered with food or milk, other manufacturers state the clinical importance of this effect is unclear, and some clinicians suggest that doxycycline, like some other tetracyclines, should not be administered with milk.
In one study evaluating doxycycline (unspecified preparation) in a limited number of healthy adults, concomitant administration of the drug with food increased the time to peak serum concentrations from 2 hours to 4 hours, but did not reduce peak serum doxycycline concentrations. In a study using doxycycline hyclate conventional capsules (Vibramycin) in a limited number of healthy adults, concomitant administration of a single 200-mg dose of doxycycline with a high-fat or high-protein meal decreased serum doxycycline concentrations by approximately 20% compared with administration in the fasting state.
In a cross-over study in healthy adult males, concomitant administration of a single 100-mg dose of doxycycline as an extended-release tablet containing doxycycline hyclate pellets (Doryx) with a high-fat, high-calorie meal resulted in a 24% decrease in mean peak serum doxycycline concentrations and a 13% decrease in the mean area under the plasma concentration-time curve (AUC) of the drug compared with administration in the fasting state. Although mean peak serum concentrations were 1.1 mcg/mL when the dose was given in the fasting state, mean peak serum concentrations were 0.87 mcg/mL when the dose was given with a high-fat, high-calorie meal. The clinical importance of this effect is unclear.
Studies evaluating the effect of concomitant administration of doxycycline and milk have given inconsistent results. In an early study evaluating doxycycline (unspecified preparation) in a limited number of healthy adults, administration with milk (without food) reduced the peak serum concentration by about 20%, but did not affect the time to peak concentrations. In a study evaluating single 200-mg doses of doxycycline as doxycycline hyclate conventional capsules (Vibramycin), there was no difference in mean serum doxycycline concentrations attained (over the first 24 hours after the dose) when the dose was given with either 150 mL of milk or water. Conversely, in another study in healthy adults, peak serum concentrations were 24% lower and the AUC was 30-35% lower when a 200-mg dose of doxycycline (soft gelatin capsules) was given with 300 mL of milk compared with administration with the same amount of water. In a study using single 100-mg doses of doxycycline conventional capsules containing the monohydrate (Vibramycin), absorption of the drug was only slightly impaired by ingestion with a glass of skim milk (peak serum concentrations 1.45 mcg/mL) compared with administration in the fasting state (peak serum concentrations 1.79 mcg/mL). However, when administered with both food and milk, peak serum doxycycline concentrations were only 1.18 mcg/mL and were not attained until 4 hours after the dose.
The effect of food and milk on GI absorption of doxycycline is less than that reported with some other tetracyclines (e.g., demeclocycline, tetracycline hydrochloride). It has been suggested that milk may have a lesser effect on GI absorption of doxycycline because the drug has higher lipophilicity and a lower affinity for calcium than these other tetracycline derivatives.