Propranolol
Propranolol. Non-selective β₁/β₂ antagonist. High lipophilicity → excellent CNS penetration — the basis for migraine prophylaxis, essential… Oral half-life 3.8 h.
Non-selective β₁/β₂ antagonist. High lipophilicity → excellent CNS penetration — the basis for migraine prophylaxis, essential tremor, and performance-anxiety uses. Black 1962 Nobel-Prize-level discovery. Infantile hemangioma indication added 2014.
PK: zero-content on all five, and the intravenous row hung on an oral-only study. Re-sourced to Ochs 1982 (PMID:7098380), 6 healthy volunteers given 20 mg intravenously and 80 mg orally in crossover: "volume of distribution, 2.3 (+/- 0.3) l/kg" (161 L at 70 kg, a TRUE volume), "elimination half-life (t 1/2 beta), 5.3 (+/- 0.6) h", "After single oral doses, t 1/2 beta (3.8 +/- 0.2 h) tended to be smaller", and "actual systemic availability (0.60 +/- 0.07)". NOTE THE SHARED 280 L WAS WRONG FOR THIS DRUG TOO — it was not a correct propranolol figure copied onto metoprolol, it was sourced for neither. F 0.60 is far above the stored 0.25 and above the textbook 25-30% because first-pass is SATURABLE and dose-dependent; it is also food- and comedication-sensitive, and no cited population is CYP2D6-genotyped, so a scalar is an approximation. EFFECT IS NOT MEANINGFULLY DECOUPLED, which is itself well evidenced: "the concentrations of antagonist present in plasma are representative of the concentrations in the effect compartment". The real complication is a stimulus-dependent potency — the concentration-effect curve shifts 2-3 fold rightward on exercise.
Pharmacokinetics
- Oral — t½ 3.8 h · F 60% · Vd 161 L
- IV — t½ 5.3 h · F 100% · Vd 161 L
Sources: PMID:1982759, PMID:15655528, PMID:7098380, PMID:3000793, PMID:2719906