Pharmakokinetik bei Kindern: Worauf kommt es bei der korrekten Medikamentendosierung an?

Zusammenfassung

Kinder sind in der Anästhesie eine seltene Patientengruppe. Um Medikamentenfehldosierungen zu vermeiden, sind genaue Kenntnisse über Aufnahme, Verteilung, Verstoffwechselung und Ausscheidung der verwendeten Wirkstoffe wesentlich. Auch bedarf es ausreichender Erfahrung mit pharmakokinetischen Variationen oder Komedikationen innerhalb der verschiedenen Altersklassen, um patientenadaptiert eine korrekte Dosisapplikation zu ermöglichen.

Abstract

Under- or overdosage of medication can lead to severe side effects in children. To avoid this, precise knowledge of age-specific liberation, absorption, distribution, metabolism and excretion – LADME for short – is necessary. Absorption can take place intravenously, orally, rectally, intranasally, transdermally or epidurally/caudally and is associated with numerous special features in children, depending on age and route of application. The distribution in children is faster due to more permeable organ barriers between individual organs and must be adapted for hydrophilic and lipophilic drugs to the patientʼs age as well as their fat and fat-free body parts. Drug biotransformation takes place through Phase I and Phase II reactions, predominantly in the liver and kidneys. The cytochrome P450 (CYP450) enzyme system is the most important system for this and requires dose adjustment for numerous drugs in the first phase of life. Due to immature kidney function, all drugs with high renal clearance have a prolonged duration of action in the first months of life. Biliary excretion is particularly important for substances with a molecular weight of > 500 g/mol and is of limited functionality during the first months of life. The amount of substrate that is eliminated by the liver and kidneys within a defined period of time is known as clearance and is strongly dependent on the substance and age of the child. Reciprocal to this is the elimination half-life, which has to be considered especially with repetitive administration. Only with sufficient experience with pharmacokinetic variations or comedications within the different age groups, a patient-adapted, individually correct dose application is possible. The knowledge of the age-specific pharmacokinetics together with the knowledge of patient-specific peculiarities and comedications allow an individual drug application characterized by heuristics.

Kernaussagen

• Körperwasser- und Fettanteil, Plasmaeiweißbindung, Herzzeitvolumen, Atemminutenvolumen, Körperoberfläche, Nieren- und Leberfunktion sind wichtige Parameter, welche die Verstoffwechselung beeinflussen.

• Insbesondere bei Früh- und Neugeborenen sind die Besonderheiten im Cytochrom-P450-Enzymsystem bei der Medikamentenauswahl und -dosierung zu beachten.

• Vor allem Substanzen mit hoher renaler Clearance unterliegen nach der Geburt einer reduzierten Exkretion.

• Die Eliminations-Halbwertszeit ist stark Substanz- und Altersabhängig und muss vor allem bei repetitiver Gabe beachtet werden.

• Genaue Kenntnisse der altersspezifischen Pharmakokinetik zusammen mit dem Wissen um patientenspezifische Besonderheiten und Komedikationen ermöglichen eine durch die Heuristik geprägte individuelle Medikamentenapplikation.

Schlüsselwörter

Kinderanästhesie - Medikamentendosierung - Pharmakokinetik - Verstoffwechselung

Key words

pediatric anesthesia - drug dosage - pharmacokinetics - metabolism

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