Prolonged Quinidine Half‐life with Associated Toxicity in a Patient with Hepatic Failure

Abstract

A markedly prolonged quinidine elimination half‐life due to hepatic failure and resultant quinidine toxicity occurred in a 57‐year‐old man with a history of atrial fibrillation. A prolonged QT interval, development of torsades de pointes, and a serum quinidine concentration of 3.1 μg/ml contributed to a decision favoring permanent pacemaker implantation. The apparent quinidine half‐life ranged from 66–99 hours and was associated with QT prolongation and persistent U waves. On discontinuing quinidine, all signs associated with toxicity resolved as serum quinidine concentrations decreased, which resulted in reversal of the decision to implant a permanent pacemaker. This case reports an extremely long quinidine elimination half‐life and reillustrates the importance of drug pharmacokinetics in patient care.

Assessment of Quinidine‐Induced Torsades de Pointes Risks Using a Whole‐Body Physiologically Based Pharmacokinetic Model Linked to Cardiac Ionic Current Inhibition

“…Co‐administrations of quinidine and erythromycin induced TdP 11 and long QT syndrome, 49 which may be partly explained by the findings that erythromycin increased plasma exposure of quinidine via inhibiting CYP3A activity 50 . Both high free fraction of plasma quinidine 51 and high plasma exposure of quinidine 52 in patients suffering from liver failure seem to explain the clinic finding that liver failure induced Tdp risks 53 …”