Pharmakokinetische Besonderheiten bei adipösen Patienten

Zusammenfassung

Adipositas und Medikamente stehen in vielfältigen Beziehungen zueinander. Einerseits induzieren viele Medikamente eine Zunahme des Körpergewichts und wirken sich ungünstig auf den Glukose- und Lipidstoffwechsel aus. Andererseits ist bei Adipositas, insbesondere bei Arzneimitteln mit kleiner therapeutischer Breite, wahrscheinlich eine Dosisanpassung vorzunehmen. Die starke Zunahme des Fettgewebes, Änderungen des regionalen Blutflusses sowie veränderte Bindung an Plasmaeiweiße sind Einflussfaktoren für das Verteilungsvolumen von Medikamenten. Darüber hinaus ist bei Adipösen der Metabolismus über Cytochrom-P450-Enzyme verändert und eine eingeschränkte Nierenfunktion häufig. Nach bariatrischer Chirurgie muss aufgrund der anatomischen und physiologischen Änderungen mit Änderungen der Pharmakokinetik und -dynamik gerechnet werden. Insgesamt stehen dem behandelnden Arzt aber nur unzureichende Daten zu Dosisanpassung bei Adipositas und insbesondere nach bariatrischer Chirurgie zur Verfügung. In diesem Artikel werden grundlegende Hinweise zur geänderten Pharmakokinetik bei Adipositas gegeben und wichtige Medikamente exemplarisch beschrieben. Anmerkungen zur besonderen Situation nach bariatrischer Operation ergänzen unsere Ausführungen.

Summary

The relationship between obesity and drugs is manifold. Several drugs induce body weight gain and interfere with glucose and lipid metabolism. In addition, dose adjustment may be required with several drugs, especially those with narrow therapeutic windows. Adipose tissue accumulation, changes in regional blood flow, and changes in plasma protein binding capacities change the volume of distribution of drugs. Additionally, cytochrome P450 enzyme activities may be changed and variations in glomerular filtration rate contribute to different pharmacokinetic properties of several drugs. Drastic weight changes with bariatric surgery again require a reevaluation of drug dosing in obese patients. Overall, there is a tremendous knowledge gap regarding dose adjustments in obesity. We will discuss the major changes in pharmacokinetics in obese patients and will discuss some drug examples. A discussion of bariatric surgery and the consequences for drug therapy will also be provided.

Schlüsselwörter

Pharmakokinetik - Verteilungsvolumen - Dosisanpassung - Cytochrom P450 - glomeruläre Filtrationsrate - bariatrische Chirurgie

Keywords

Pharmacokinetics - volume of distribution - dose adjustment - cytochrome P450 - glomerular filtration rate - bariatric surgery

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