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Doxycycline, once a staple of antibiotics, had become a major concern for the health care industry: it was the only antibiotic approved by FDA that is metabolized CYP3A4 (see ). This was the second time it had been discovered that a medication metabolized by this gene has adverse effects. The first time was with penicillin, which developed in the 1920s. Although drug was approved in 1951, it took nearly 25 years before the drug's use was stopped because of the widespread use drug (see ). The CYP3A4 gene mutation in Doxycycline is common among individuals who take antibiotics, and the FDA did not take this into account when prescribing it. The fact that this drug causes CYP3A4 enzyme activity to become increased has raised a great deal of concern among physicians and drug manufacturers. CYP3A4 enzyme activity is one of the factors that determine therapeutic effects of drugs, both orally and intravenously. In particular, a low-dose, high-efficacy drug like Doxycycline can cause a significant increase in the body's CYP enzymes. A low-dose, high-efficacy drug like Doxycycline can have adverse reactions, including severe gastrointestinal problems, that are not seen with the more typical CYP3A4-mediated effects (see ).
Figure 1. CYP3A4: Effects of Doxycycline on the Body.
Doxycycline causes a substantial increase in blood levels of the enzyme cytochrome P450 (CYP) 3A4. CYP3A4 is part of the "enzymatic machinery" needed to break down other drugs. In its absence, an individual can receive the adverse effects of these drugs without receiving the drug's therapeutic effects.
The drug's use in humans has been limited because most patients develop a significant reduction in the level of CYP3A4, including a large decrease in the activity of this enzyme. Patients who experience a moderate reduction in CYP3A4 activity are prescribed lower doses of this drug or discontinued altogether. The severity of enzyme's reduction is determined by both genetic makeup and the presence of other drugs generic adderall xr that stimulate the enzyme. When drug is metabolized by CYP3A4 and
adderall in deutschland bestellen other drug metabolizing enzymes, a large range of effects can occur. For example, the drug's metabolism by CYP3A4 can produce a variety of pharmacologic effects including decreased drug metabolism for Adderal 90 pills $344.45 $3.83 a given concentration of the drug. CYP3A4 inhibition has also caused a dramatic decrease in the level of several drugs, including some types of antibiotics. This is a major concern because these drugs are widely used with an increasing frequency in people who are hospitalized or very ill.
Figure 2. Effect of the CYP3A4 Gene on Drug Reactions.
When these drugs are taken in larger doses than the amount that is needed to prevent adverse drug effects, they can have severe and potentially life-threatening consequences.
The CYP3A4 enzyme can function for several days after the medication has been given (see ).
There is no specific way to predict which medicines, including antidepressants, are likely to increase or decrease activity of the CYP3A4 enzyme. This enzyme
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A CYP3A4 inhibitor, like Doxycycline, can be prescribed as a single dose or maintenance therapy over several days. Patients can also be monitored for CYP3A4 function by monitoring blood samples.
The CYP3A4 enzyme can also have a profound effect on other drugs when it is active, such as antibiotics. A decrease in CYP3A4 activity can produce serious drug toxicity; in some cases, patients are unable to metabolize the antibiotic at same potency as when the drug was given.
The FDA recently approved a drug that can increase the activity of CYP3A4 enzyme and make it more effective. Its name is "Dyldaxone" and
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