[Drug interactions and immunosuppression  in organ transplant recipients].
BACKGROUND
Immunosuppressive drugs are used to prevent rejection following organ transplantation. Most immunosuppressive drugs have narrow therapeutic concentration ranges. This increases the probability of clinically relevant drug interactions. In the following, we provide an overview of drug interactions that may be of importance to immunosuppressive treatment.


METHODS
Data on the interaction of immunosuppressant drugs was obtained by means of a non-systematic literature search in PubMed. Articles were selected on the basis of their clinical relevance.


RESULTS
The literature is primarily concerned with pharmacokinetic interactions. Calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (sirolimus, everolimus) are particularly susceptible to the effects of substances that inhibit or induce cytochrome P450 (CYP) 3A4 and P-glycoprotein. These interactions may lead to the levels of the immunosuppressive drugs in blood altering by a factor of more than 10. Methylprednisolone and prednisolone may also be affected by substances that modulate CYP3A4 and P-glycoprotein. The level of mycophenolate is lowered by simultaneous use of some proton pump inhibitors, antibiotics and anion binders, and by valproic acid and rifampicin. Some immunosuppressive drugs also interact with one another: cyclosporine raises the level of mTOR inhibitors and lowers the level of mycophenolate. In general, the degree of pharmacological interaction will vary from one individual to the next.


CONCLUSIONS
In the event of an expected clinically relevant drug interaction, frequent measurements of the concentrations of the drug in question are a good means of achieving individual adjustment of the immunosuppressant treatment. Prior knowledge of drug interactions can thereby contribute to prevent undesirable changes in the immunosuppressant effect.
Avdeling for medisinsk biokjemi, Oslo universitetssykehus, Norway. nils.tore.vethe@oslo-universitetssykehus.no
Nils Tore
NT
Vethe
Karsten
K
Midtvedt
Anders
A
Asberg
Rune
R
Amundsen
Stein
S
Bergan
D019703:Calcineurin / Q000493:pharmacokinetics; D065095:Calcineurin Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D008775:Methylprednisolone / Q000493:pharmacokinetics; D009173:Mycophenolic Acid / Q000493:pharmacokinetics; D016377:Organ Transplantation; D011239:Prednisolone / Q000493:pharmacokinetics; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D011239:Prednisolone; D051544:Cytochrome P-450 CYP3A; D058570:TOR Serine-Threonine Kinases; D019703:Calcineurin; D009173:Mycophenolic Acid; D008775:Methylprednisolone