Dofetilide
Dofetilide. Class III antiarrhythmic — selective IKr blockade prolongs cardiac repolarization. Approved for AF rhythm control. Mandatory 3-day… Oral half-life 8 h.
Class III antiarrhythmic — selective IKr blockade prolongs cardiac repolarization. Approved for AF rhythm control. Mandatory 3-day inpatient initiation (TdP risk during loading); strict CrCl-based dosing + numerous CYP3A4 / OCT2 inhibitor contraindications.
PK: F 0.92 is verbatim and stands. The volume and half-life are re-sourced to PMID:1958435, which gives "clearance (23 l h-1), terminal elimination half-life (8 h) and volume of distribution (245 l)" in one sentence from one intravenous cohort — the stored 10 h was the upper endpoint of a review range, and the stored set was internally inconsistent, its own clearance and half-life implying 353 L rather than 250. ka 1.5 appears in no dofetilide abstract and is byte-identical to the value MEXILETINE carried, from an unrelated paper that also states no rate. THE EFFECT COMPARTMENT IS REMOVED, and the reason is subtle enough to record: its value verified perfectly — right quote, right arithmetic, species correctly named as beagle dog — but it was measured under INTRAVENOUS infusion, and in humans on the ORAL route the same relationship is direct: "a counterclockwise hysteresis loop ... was observed after intravenous infusions in all subjects, whereas direct linear relationships were observed after oral administrations in eight of 10 subjects", with peak effect coinciding with peak concentration. This record is oral-only, so a dog intravenous value imposed a delay the human oral data says is not there. Its stated precision was also 11 plus or minus 8 minutes, a sixfold band stored as a point.
Pharmacokinetics
- Oral — t½ 8 h · F 92% · Vd 245 L
Sources: PMID:1958435, PMID:10971309