Should antibiotics be taken with food
Medicines before, during or after the meal?
The interactions between food and drugs can be roughly divided into pharmacokinetic and pharmacodynamic interactions. The latter increase or decrease the effectiveness of the drug. However, most interactions with food are of a kinetic nature, i.e. changes in absorption, distribution, storage, binding, metabolism or excretion change the course of the concentration of the drug in the blood over time.
Food delays the passage through the stomach
If medicines are taken with food, they stay in the stomach longer and later reach the intestines. Due to its large internal surface, this is the main absorption site for most drugs. This effect is increased by high-fat foods, as this food stays in the stomach longer. This must be taken into account in particular in the case of monolithic gastric juice-resistant dosage forms. This is because the stomach preferably releases particles 1 to 2 mm in size to the intestine. Only when the stomach is empty presses larger particles into the intestine. An enteric-coated tablet remains in the stomach until all of the food has left the stomach and only then reaches the intestines. Taking it with food can delay the onset of action by three to six hours. Such tablets should therefore be taken with plenty of water about an hour before a meal. However, this recommendation does not have to be observed for enteric-coated pellets in gastric juice-soluble capsules.
Analgesics flood quickly on an empty stomach
The delay in absorption through ingestion of food is particularly important in the case of analgesics. Acetylsalicylic acid, paracetamol and ibuprofen in combination with food reach significantly lower plasma concentrations than fasting. However, the overall bioavailability remains unchanged. If a rapid influx is desired to treat acute pain, analgesics should therefore be taken on an empty stomach if possible. In addition, pain reduces gastric motility, which further impairs the transport of the drug into the intestine. These effects speak for the use of effervescent tablets. However, the rapid onset of action must be weighed against the disadvantages of the mucosal tolerance of the analgesics, especially acetylsalicylic acid. Therefore, the individual tolerance must be observed.
Change in bioavailability
Effects on bioavailability, i.e. more or less active ingredient becomes available, are even more common than the reduction in the rate of absorption of a drug through food intake. In addition, the maximum plasma concentration reached can be higher or lower than without food. This is particularly important for active ingredients with a narrow therapeutic window. This is because the minimum toxic concentration can be exceeded or the minimum therapeutic concentration can be undershot. There can be many reasons for the decreased bioavailability of drugs when they are eaten at the same time. Acid-labile active ingredients are broken down more strongly due to the longer retention time in the stomach. Other drugs can be adsorptively bound to the food or form poorly soluble complexes with polyvalent metal ions. Some foods activate the metabolism of drugs.
Antibiotics are usually beneficial before meals
Penicillin V and ampicillin are examples of drugs whose bioavailability is greatly reduced by food. They should therefore be given on an empty stomach. This restriction does not apply to amoxicillin. Most antibiotics are recommended to be taken with sufficient fluids about an hour before a meal. This results in shorter retention times in the intestine and thus less damaging effects on the intestinal flora. In addition, high blood level peaks occur, which also damage less sensitive pathogens that have a higher minimum inhibitory concentration. However, substance-specific peculiarities have to be observed with many antibiotics. Most cephalosporins can also be taken with food. This is even recommended for prodrugs. Exceptions are Ceftibuten and Cefalexin, which should be taken before eating. The absorption of cefaclor and loracarbef is delayed by food, but the effect is considered to be tolerable.
Different erythromycin salts
The bioavailability of erythromycin base and stearate is significantly reduced by food. These acid-labile substances are largely converted during the extended gastric passage. The double formation of acetals creates a new active ingredient that acts as a motilin agonist and causes gastrointestinal complaints. In contrast, erythromycin ethyl succinate, estolate, stinoprate and lactobionate are not sensitive to acids. Their bioavailability increases even in connection with food. They can therefore be given well to eat.
The newer macrolides are not inactivated by acid and do not form motilin agonists. This is how clarithromycin can be taken with food. With roxithromycin, food has little impact on bioavailability. It should therefore be taken before eating. Lincomycin is another example of an antibiotic with relevant interactions with food. This should be taken at least one hour before eating, and according to some authors even further away from food.
Polyvalent metal ions form chelate complexes
Many drugs can be complexed with multivalent cations such as calcium, magnesium, iron or aluminum ions. Calcium is particularly important in practice because it is contained in relevant quantities in dairy products and calcium-fortified foods. The polyvalent metal ions can form chelate complexes that may even precipitate on the mucosa. This particularly applies to tetracycline. The effect is less with doxycycline and minocycline. However, all tetracycline derivatives should be taken without dairy products and other calcium-rich foods. Tetracycline and oxytetracycline should be taken on an empty stomach, doxycycline and minocycline with food, as this improves tolerability. The older fluoroquinolones are also affected by calcium ions. With the newer substances the effect is less, with the newest ones like Sparfloxacin the problem does not apply. However, it can generally be recommended to take gyrase inhibitors on an empty stomach. Norfloxacin and ciprofloxacin should not be taken with dairy products or other calcium-rich foods.
Special features of bisphosphonates
Apart from these antibiotics, bisphosphonates in particular are very sensitive to calcium. The already low bioavailability of bisphosphonates is generally further reduced by food and especially by polyvalent metal ions. They should therefore be taken with water only about two hours before eating, if possible. Because of their ulcerogenic effect, an upright posture should be maintained for at least half an hour after taking bisphosphonates.
Tannins react with many substances
In addition to metal ions, tannins are other food components that often interact with drugs. They have a high affinity for basic nitrogen and can precipitate alkaloids. Therefore, if possible, drugs should not be taken with beverages containing tannin, such as tea or fruit juices, but only with water. This also applies to iron supplements, the already low bioavailability of which is further reduced by tannins. Iron should also not be combined with foods that are high in oxalate, such as rhubarb or spinach, or phosphate. With these anions, iron forms compounds that are difficult to dissolve.
Fiber isn't all good
Dietary fiber, as a food component, is also problematic for the absorption of various medicinal substances. The delayed or reduced absorption of paracetamol, penicillins and trimethoprim in connection with dietary fiber has been described. The plasma levels of doxepin and desipramine were significantly reduced. The decrease in the bioavailability of levothyroxine is particularly pronounced. This is normally used long-term by an enterohepatic cycle, which is however interrupted by fiber. The otherwise very long half-life of levothyroxine is thus significantly reduced.
Food can also increase bioavailability
In contrast to the drugs mentioned so far, there are other substances whose bioavailability increases through simultaneous food intake. In this way, poorly soluble drugs dissolve better during a longer stay in the stomach. Food rich in fat can improve the absorption of lipophilic drugs, among other things through the increased secretion of solubilizing bile acids. This effect increases the bioavailability of etretinate many times over, for example. The bioavailability of acitretin, isotretinoin, chloroquine, mefloquine, halofantrine, cyclandelate, itraconazole and nitrofurantoin also increases in connection with food intake. In general, lipophilic drugs should preferably be taken with food, provided that the bioavailability does not increase in an extreme way. In addition, this recommendation can reduce gastrointestinal side effects. However, in some cases the peak concentrations are difficult to control, so that toxic levels can be reached. The longer intestinal passage in connection with food also offers more time for absorption. This improves the absorption of some antibiotic prodrugs, such as erythromycin estolate and ethyl succinate, which behave in the opposite way to the erythromycin base. With some drugs, the simultaneous consumption of protein-rich foods can reduce the first-pass effect, as the liver enzymes are saturated by the food. Then the plasma concentration of the drug is only slightly reduced during the first passage through the liver. Therefore, e.g. propafenone, ticlopidine and vinpocetine should always be taken with food.
In addition, the bioavailability of drugs increases when their degradation is inhibited. Very many drugs are completely or predominantly metabolized by just one of the more than 30 known isozymes of cytochrome P-450. For example, the inhibition or saturation of the respective isoenzyme by a food component can largely prevent the metabolism of the medicinal substance and thus increase its bioavailability almost dramatically. A typical and well-known example of this is grapefruit juice, which inhibits the isoenzyme CYP3A4. This is also present in the intestinal mucosa and normally already reduces the concentration of some medicinal substances there. The effect was first described for felodipine, the plasma concentration of which increases many times over by grapefruit juice. Relevant increases in bioavailability through grapefruit juice have meanwhile been described for nifedipine, nicardipine, nitrendipine, nisoldipine, nimopidine, terfenadine, saquinavir, cyclosporine, midazolam, triazolam and verapamil, among others. Therefore, drugs should not be taken with grapefruit juice.
Accurate predictions remain impossible
It does not make sense to specifically increase the bioavailability of medicinal substances with grapefruit juice. Like most of the other interactions shown here, this effect is subject to strong inter-individual fluctuations and is therefore difficult to estimate. Houses also emphasized that all statements made result from investigations of clinical parameters. This would leave their therapeutic effect unexplained, but this has only rarely been investigated so far. A significant influence should not generally be assumed. Many studies also show contradicting effects. This mostly suggests an interplay of several influencing factors. In addition, the results of studies should not be transferred to chemically closely related drugs, as completely different relationships can apply to these. Furthermore, studies on bioavailability are generally carried out on healthy volunteers. It remains to be seen to what extent the disease to be treated influences the bioavailability of the drugs. Ultimately, in addition to the interactions, compliance would have to be considered. Here, the recommendation to take with food often proves to be advantageous, as the drug is not forgotten and this often improves willingness to take.
The most important contents in brief:
JAll solid oral dosage forms should be taken with at least 100 to 200 ml of water, unless larger amounts are necessary in special cases. If possible, other drinks should not be used for ingestion.
- Monolithic gastric juice-resistant dosage forms should be taken on an empty stomach at least one hour before eating.
- If a quick effect is desired, drugs should be taken on an empty stomach.
- Most antibiotics should be taken an hour before a meal, and some can be taken with food.
- Bisphosphonates should be taken in an upright position with plenty of water two hours before eating.
- Lipophilic drugs should be taken with food.
- Foods rich in tannins and calcium should not be consumed in connection with medicinal products.
- The therapeutic consequences of the bioavailability data are mostly insufficiently known.
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