Pharmacokinetics (PK) is the journey of a compound through your body — summarized as ADME.
- Absorption — how it gets in. Oral, sublingual, injection (subcutaneous/intramuscular/IV), transdermal, nasal. Peptides are usually injected because stomach acid destroys them (this is why BPC-157 and semaglutide are shots, not pills — and why oral semaglutide needs a special absorption enhancer).
- Distribution — where it goes. Fat-soluble compounds reach the brain and store in fat; water-soluble ones stay in blood.
- Metabolism — how it's broken down, mostly by liver CYP450 enzymes (e.g., CYP3A4). This is the source of most drug interactions: one compound speeding up or blocking a CYP enzyme changes the levels of another. This is why the entries flag "CYP3A4 inhibitor."
- Excretion — how it leaves (kidney/urine, bile/stool).
Key derived concepts:
- Bioavailability — the fraction that actually reaches your bloodstream. Oral arginine has low bioavailability (destroyed first-pass in the liver) — which is exactly why citrulline, which converts to arginine after the liver, works better. Understanding bioavailability explains dozens of "why this form over that form" choices.
- First-pass metabolism — everything absorbed from the gut hits the liver first, which can destroy most of an oral dose before it circulates.
- Half-life — the time for blood levels to halve. Caffeine's ~5–6 h half-life is why an afternoon coffee wrecks sleep; modafinil's 12–15 h is why it must be taken on waking. Half-life sets dosing frequency and timing.
- Steady state — with repeated dosing, levels plateau after ~5 half-lives. Why beta-alanine "loads" over weeks and creatine saturates in days.
✅ Key takeaways
- Pharmacokinetics is the ADME journey: Absorption, Distribution, Metabolism, Excretion.
- Bioavailability = the fraction that reaches your blood; first-pass liver metabolism destroys much of an oral dose (why citrulline beats arginine).
- Half-life sets dosing timing — caffeine's 5–6 h is why an afternoon coffee wrecks sleep; levels reach steady state after ~5 half-lives.
- Most drug interactions come from CYP450 liver enzymes: one compound speeding up or blocking a CYP changes another's blood levels.
🧠 Check yourself
Q1 Why is oral arginine weak but citrulline effective for the same 'pump' goal?
Arginine is largely destroyed first-pass in the liver (low bioavailability). Citrulline converts to arginine AFTER the liver, so more reaches the blood.
Q2 Caffeine's half-life is ~5–6 h. What does that predict about a 4pm coffee?
Roughly half is still circulating at 9–10pm, disrupting sleep. Half-life sets timing.
Q3 What does ADME stand for?
Absorption, Distribution, Metabolism, Excretion — the compound's journey through the body.