Metoprolol
Metoprolol. Cardioselective β₁ blocker. Short-acting tartrate for acute BP/HR control; long-acting succinate for HFrEF (MERIT-HF trial). CYP2D6… Oral half-life 4.2 h.
Cardioselective β₁ blocker. Short-acting tartrate for acute BP/HR control; long-acting succinate for HFrEF (MERIT-HF trial). CYP2D6 substrate — major interaction source.
PK: zero-content on all five; the intravenous row hung on a single-oral-dose study. Re-sourced: V 175 L from Schaaf 1987 (PMID:3443140), verbatim "smokers (S) and nonsmokers (NS) was that S had a larger steady-state volume of distribution (3.3 vs 2.5 l/kg)" — the non-smoker figure, an intravenous-infusion steady-state volume; half-life 4.2 h and F 0.50 from Regardh 1981 (PMID:7333059), verbatim "The mean fraction of the drug available systematically was 84 +/- 10% in patients and 50 +/- 11% in a control group of 6 healthy subjects" (the healthy-control arm, NOT the cirrhotic one). A SINGLE SCALAR BIOAVAILABILITY IS EMPHATICALLY WRONG HERE: clearance differs more than ten-fold between CYP2D6 poor and ultrarapid metabolisers (31 against 367 L/h), between-subject F spans 15 to 92%, and first-pass is saturable, F rising from 31% to 46% between 20 and 100 mg. BUT THE EFFECT IS BUFFERED AGAINST THAT: despite the ten-fold clearance spread, pharmacodynamics "differed only by less than 2-fold", so a model predicting effect from the plasma curve will overstate the genotype spread roughly five-fold.
Pharmacokinetics
- Oral — t½ 4.2 h · F 50% · Vd 175 L
- IV — t½ 4.2 h · F 100% · Vd 175 L
Sources: PMID:1982759, PMID:17420778, PMID:10895074, PMID:7333059, PMID:3443140, PMID:6114930