Quinidine
Quinidine. Class IA antiarrhythmic + Na+ + K+ channel blocker; also potent CYP2D6 + P-glycoprotein inhibitor → classic raises-digoxin example.… Oral half-life 10 h.
Class IA antiarrhythmic + Na+ + K+ channel blocker; also potent CYP2D6 + P-glycoprotein inhibitor → classic raises-digoxin example. Dextrorotatory stereoisomer of quinine. Largely supplanted by safer antiarrhythmics.
PK: the best-cited record in its group. The oral half-life 10.34 h is verbatim and stands, as does the effect-compartment value. F 0.7 is exactly right but belonged to Guentert 1979 (PMID:512840), not the cited interaction study — verbatim "The mean oral bioavailability of quinidine was 0.70 +/- 0.17" — and that paper also supplies a true intravenous volume, "Vdarea: 2.53 +/- 0.72 liter/kg" (177 L at 70 kg). The stored 200 L appears nowhere; the only volume in the CITED abstract belongs to DIGOXIN. The intravenous row now carries 5.7 h, the value measured after intravenous dosing, since 10.34 h is an oral steady-state figure. ABSORPTION IS ZERO-ORDER, stated outright: "Absorption was in most cases best described by a zero-order rather than by a first-order process" — so the stored rate was structurally wrong, not merely uncited. F 0.70 is an oral SOLUTION figure; sustained-release tablets differ (78-87%). Three references are CYP2D6-inhibition studies containing no quinidine pharmacokinetics. INTERACTIONS: TWO OF FOUR INVERT THROUGH 1.5 µM — the dextromethorphan edge, whose source is the same paper this catalogue cites for dextromethorphan own pharmacokinetics, and propafenone. THE DIGOXIN EDGE IS LEFT ALONE FOR A REASON WORTH STATING: it does not fit the constant, and it is P-GLYCOPROTEIN INHIBITION rather than enzyme inhibition, so a competitive-inhibition affinity is a borrowed shape there regardless of what number sits in it. The desipramine edge implies a rise its visible note does not state.
Pharmacokinetics
- Oral — t½ 10.3 h · F 70% · Vd 177 L
- IV — t½ 5.7 h · F 100% · Vd 177 L
Related compounds
- Digoxin — major
- Dextromethorphan — major
- Propafenone — caution
- Desipramine — major
Sources: PMID:8471402, PMID:12086981, PMID:9413244, PMID:8841152, PMID:2719900, PMID:2792169