The medicamentous interaction results from the successive administration concomittante or from two or several Médicaments being able to lead to serious consequences for the health of the patient.

On the level of the Pharmacokinetic , the administration of two drugs metabolized consequently way (for example, the cytochrome P450 3A4, or quite simply CYP3A4) will have consequences on the clearance of these drugs.

A figure, to show the extent of the phenomenon and its gravity in France, country where one consumes in the world the most drugs, it is true: there would be, according to the Ministry for Health, 8.000 annual deaths of the only fact of the medicamentous interactions

Medicamentous interactions dependant on the Pharmacokinetic

Absorption

Acceleration of absorption

Deceleration of absorption

Distribution

Metabolism

Inhibition of the metabolism

For example, if one manages a drug Inhibiteur of a way of metabolisation given and that one manages also a drug which is a Substrat of this same way, the molecule substrate will see his decreased clearance, his increased half-life, his volume of distribution increased and, consequently, its plasmatic Concentration will increase with the passing days, which will be able to result in more important Undesirable effects. An example of this mechanism is the medicamentous interaction between the Clarithromycine (Biaxin®), an inhibiting antibiotic of the CYP3A4, and the Atorvastatine (Lipitor®), a substrate of the CYP 3A4. The administration concomittante of these two drugs involves an increase in the Biodisponibilité of the atorvastatine and increases in a clinically significant way the risk of Rhabdomyolyse ^1,2.

Induction of the metabolism

On the other hand, if one manages a drug Inducteur of a way of metabolisation given and that one manages also a drug which is a substrate of this same way, the molecule substrate will see his clearance increasing, his biodisponibility to decrease and, consequently, its plasmatic concentration will decrease with the passing days and its effectiveness will decrease. In the case of the antibiotics, this interaction is catastrophic, because that can frequently lead to failures of treatment. An example of this mechanism is the medicamentous interaction between the Cyclosporine (Sandimmune® or Neoral®), a immunosuppressor used in the anti-rejections treatments, and the Millepertuis, a natural health product. The millepertuis is an inductor of the CYP3A4, and the cyclosporine is a substrate. The administration concomittante of these two drugs decrease by 46% the biodisponibility of the cyclosporine after only 14 jours^1,2. The consequence? The rejection of the transplanted body.

Elimination

Increase in the elimination of the drug

Deceleration of the elimination of the drug

Medicamentous interactions dependant on the mechanism of action

By additive pharmacological effect

By contrary pharmacological effect

Medicamentous interactions and pharmacothérapie

The interactions medicamentous are one of the 8 problems connected to the Pharmacothérapie. It is important to regulate them to optimize the therapy of a patient, and the pharmacist is the health professional best trained to work with the pharmacothérapie of a patient.