{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:46:22Z","timestamp":1697175982034},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,7]],"date-time":"2013-03-07T00:00:00Z","timestamp":1362614400000},"content-version":"vor","delay-in-days":2622,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2006,1]]},"abstract":"<jats:p>Population pharmacokinetics (PK) of a sodium channel\u2014blocking antiarrhythmic, pilsicainide, was studied using the nonlinear mixed\u2010effects modeling technique in 91 patients with cardiac arrhythmias (80 suspected Brugada syndrome [BrS] and 11 with atrial fibrillation) who received an intravenous infusion of 10 mg of the drug. Population pharmacodynamic (PD) analysis was also performed using an effect compartment model. PD responses were assessed by changes in electrocardiogram (ECG) pattern (BrS\u2010like elevation of ST\u2010segment) and conduction parameters. The final PK model showed that gender (values were 50% lower in women than in men) and creatinine clearance were significant (<jats:italic>P<\/jats:italic> &lt; .01) covariates of weight\u2010normalized systemic clearance of pilsicainide. Patients who showed a BrS\u2010like ECG pattern after the drug administration also showed a significantly (<jats:italic>P<\/jats:italic> &lt; .01) greater prolongation in His\u2010Purkinje conduction compared to the remaining patients. In conclusion, female gender, renal dysfunction, and the drug\u2010induced BrS\u2010like ECG morphology may be associated with augmented ECG responses to pilsicainide.<\/jats:p>","DOI":"10.1177\/0091270005283281","type":"journal-article","created":{"date-parts":[[2006,1,5]],"date-time":"2006-01-05T23:48:39Z","timestamp":1136504919000},"page":"59-68","source":"Crossref","is-referenced-by-count":5,"title":["Population Pharmacokinetic and Pharmacodynamic Analysis of a Class IC Antiarrhythmic, Pilsicainide, in Patients With Cardiac 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