Ranolazine
Ranolazine. Late sodium current (INa-late) inhibitor in cardiomyocytes — reduces Ca²⁺ overload and improves diastolic function. Anti-anginal… Oral half-life 7 h.
Late sodium current (INa-late) inhibitor in cardiomyocytes — reduces Ca²⁺ overload and improves diastolic function. Anti-anginal without significant heart-rate or BP effects. CYP3A4 + P-gp substrate; QT prolongation modest. Mild HbA1c reduction signal.
PK: THE HALF-LIFE IS RELEASE-LIMITED, AND ITS OWN LITERATURE SAYS SO IN ONE SENTENCE: "Elimination half-life of ranolazine is 1.4-1.9 hours but is apparently prolonged, on average, to 7 hours for the ER formulation as a result of extended absorption (FLIP-FLOP KINETICS)". So the disposition value is about four times shorter, and the stored 7 h is retained only as the extended-release apparent value, now labelled. It also collided with its cited paper "500 mg twice daily for 7 DAYS", that paper actually reporting 6.4, 6.4, 6.7 and 6.28 h. V 180 L was the UPPER BOUND of a stated "85 to 180 L", and F 0.55 lay OUTSIDE the stated "35% to 50%" entirely; the lower endpoint is now carried. ELIMINATION IS SATURABLE — clearance falls from 45 to 33 L/h between 500 and 1000 mg twice daily — so no single clearance holds across the dose range. ka 0.4 dropped.
Pharmacokinetics
- Oral — t½ 7 h · F 35%
Sources: PMID:23355361, PMID:16640453