Caffeine pharmacokinetics

Absorption

• Caffeine is rapidly absorbed through the gastrointestinal tract.
• Peak plasma levels occur 30–60 minutes after ingestion.
• Bioavailability is nearly 100%, meaning almost all ingested caffeine enters circulation.

Distribution

• Caffeine is water- and lipid-soluble, allowing it to cross biological membranes.
• Easily crosses the blood-brain barrier, where it exerts stimulating effects.
• Volume of distribution: ~0.6 L/kg, meaning it disperses widely in body tissues.

Mechanism of Action

• Primary effect: adenosine receptor antagonism.
• By blocking adenosine (a sleep-promoting neurotransmitter), caffeine increases alertness, reduces fatigue, and enhances focus.
• Also increases release of neurotransmitters (dopamine, norepinephrine).

Metabolism

• Metabolized mainly in the liver by enzyme CYP1A2 (cytochrome P450 system).
• Major metabolites:
• Paraxanthine (80%) → increases lipolysis and free fatty acid release.
• Theobromine (10%) → vasodilator, smooth muscle relaxant.
• Theophylline (4%) → bronchodilator.

Half-Life

• Average elimination half-life: 3–6 hours in adults.
• Influenced by:
• Genetics (fast vs slow metabolizers of CYP1A2).
• Age (slower in infants, faster in adolescents).
• Pregnancy (half-life increases significantly in 2nd/3rd trimester).
• Smoking (induces metabolism, shortens half-life).
• Medications (oral contraceptives, SSRIs, antifungals prolong half-life).

Excretion

• ~1–2% excreted unchanged in urine.
• Rest eliminated as metabolites.

Practical Implications

• Most individuals feel caffeine’s stimulating effects within 15–30 minutes.
• Late-day consumption can disrupt sleep due to 6+ hour half-life.
• Genetic differences explain why some people tolerate caffeine well while others experience jitters or insomnia.

Summary

Caffeine pharmacokinetics involve rapid absorption, wide distribution (including the brain), hepatic metabolism via CYP1A2, and renal excretion. Half-life varies widely, explaining individual differences in sensitivity and tolerance to coffee.

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• Practical Implications