Pharmacokinetic and Pharmacodynamic Effects of Caffeine

Pharmacokinetic and Pharmacodynamic Effects of

Caffeine

Ursula Gundert-Remy Guest Professor, Medical School, Berlin, Guest Scientist at the Federal Institute for Risk Assessment (BfR), Berlin

EFSA STAKEHOLDERS MEETING ON THE SAFETY OF CAFFEINE Brussels, 5 March 2015

PHARMACOKINETIC

Pharmacokinetic and Pharmacodynamic Effects

Absorption and distribution

? Rapid (tmax 30 - 120 min) and complete absorption ? Crosses freely blood-brain, placental and testicular barrier ? Volume of distribution (~ 0.67 L/kg bw) ? No specific tissue accumulation

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PHARMACOKINETIC

Pharmacokinetic and Pharmacodynamic Effects

Metabolism/Excretion - General

? Main route of metabolism in humans (70-80 %): N-3 demethylation to paraxanthine (1,7-dimethylxanthine, 17X) catalysed by cytochrome (CYP) 1A2 in the liver.

? Other primary metabolites are theophylline and theobromine.

? Smaller proportion is metabolised by CYP3A4, xanthine oxidase and N-acetyltransferase 2.

? Plasma half-life in adults about 2 - 8 hrs

? Linear kinetic up to at least 7.1 mg/kg in adult

? Paraxanthine, theophylline and theobromine are further metabolized and then excreted in the urine.

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PHARMACOKINETIC

Pharmacokinetic and Pharmacodynamic Effects

Metabolism ? variability factors

minor

? Age

? Genetic factors: o Men with higher CYP1A2 enzyme activity than women o genetic polymorphism of CYP1A2

? Life-style factors o caffeine intake (>2 cups of coffee/d) > CYP1A2 activity o smoking > CYP1A2 activity o Contraceptives > CYP1A2 activity

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PHARMACOKINETIC

Pharmacokinetic and Pharmacodynamic Effects

Metabolism ? variability factors Major ? Pregnancy > CYP1A2 activity

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