Methotrexat

Zusammenfassung

Methotrexat (MTX) spielt eine Schlüsselrolle in der Therapie der rheumatoiden Arthritis (RA) und besitzt besondere pharmakologische Eigenschaften. Die orale Gabe hat im Gegensatz zur parenteralen durch eine variable intestinale Aufnahme und die Bildung eines Plateaus der Bioverfügbarkeit bei einer Dosis von ca. 15 mg/Woche Nachteile. Der Aktivierungsschritt der intrazellulären Polyglutamierung, der bei der subkutanen Gabe deutlicher nachweisbar ist, bestimmt wesentlich die Kinetik der Wirkung von MTX. Die Kombinationstherapie von MTX mit einem Biologikum wirkt vor allem durch die Hemmung der Antikörperbildung gegen den Kombinationspartner. Dabei sind im Vergleich zur Monotherapie schon kleinere Dosen ausreichend wirksam. Der Effekt von MTX auf eine Reduktion der kardiovaskulären Mortalität bei RA wurde immer wieder gezeigt. Neue Untersuchungen lassen vermuten, dass dieser Effekt teilweise unabhängig von der Wirkung auf die Krankheitsaktivität der RA sein könnte.

Summary

Methotrexate (MTX) plays a key role in treatment of rheumatoid arthritis (RA) and has specific pharmacological properties. In contrast to injections, the oral application has a diminished effect due to variable resorption and a plateau of bioavailibility at about 15 mg/week. The activation step of intracellular polyglutamation, which is stronger after subcutaneous application, explains the kinetics of MTX effects in patients. Combination treatment of MTX with an biologic drug mainly acts trough inhibition of antibody formation against the combination partner. For this effect, in comparison to monotherapy, smaller doses of MTX are sufficient effective. The effect of MTX on reduction of cardiovascular mortality has been shown repeatedly. Current investigations lead to the hypothesis, that this protective effect may be independent from its effect on disease activity of RA.

Schlüsselwörter

Methotrexat - rheumatoide Arthritis - Pharmakologie - Mortalität - Anti-Drug-Antikörper

Keywords

Methotrexate - rheumatoid arthritis - pharmacology - mortality - anti-drug-antibody

• Literatur

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