Propafenone
Propafenone. Class IC antiarrhythmic — Na+ channel blocker with weak β-blocker activity. "Pill-in-pocket" cardioversion of paroxysmal AF in… Oral half-life 5.5 h.
Class IC antiarrhythmic — Na+ channel blocker with weak β-blocker activity. "Pill-in-pocket" cardioversion of paroxysmal AF in structurally normal hearts. CYP2D6 substrate (~7% poor metabolizers have higher levels + more β-blockade). Pro-arrhythmic in ischemic heart disease.
PK: F 0.1 appears in NO propafenone abstract. Three candidate origins are logged as hypotheses: a FOLD-CHANGE ("a 10-fold increase in drug concentration"), a PATIENT COUNT ("in 10 subjects"), or — most interesting — DIPRAFENONE, a different drug whose paper reports "bioavailability from 10.9 ... to 32.5%". A SCALAR BIOAVAILABILITY IS NOT DEFENSIBLE HERE AT ALL: first-pass is saturable, a threefold dose rise producing a tenfold concentration rise, and oral clearance splits 4.2-fold by CYP2D6 phenotype. The measured absolute value of 15.5% is stored with that caveat. The stored 6 h half-life is an EXTENSIVE-METABOLISER value in all but name — poor metabolisers are 17.2 h, a threefold split — and 5.5 h is now stored from the genotyped study. V 252 L is the same number the record had, re-sourced to the paper that actually states it as an intravenous-derived steady-state volume. ACTIVE METABOLITE MAKES PARENT-ONLY KINETICS ROUTE-DEPENDENT: 5-hydroxypropafenone is present in nine of ten extensive metabolisers and neither poor metaboliser.
Pharmacokinetics
- Oral — t½ 5.5 h · F 16% · Vd 252 L
Sources: PMID:6872170, PMID:3829342, PMID:6744775