{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T22:44:03Z","timestamp":1759099443476},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,3,8]],"date-time":"2013-03-08T00:00:00Z","timestamp":1362700800000},"content-version":"vor","delay-in-days":4449,"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":[[2001,1]]},"abstract":"<jats:p>The pharmacokinetics (PK) of the antiarrhythmic sotalol, which elicits Class III and beta\u2010blocking activity, has not been adequately defined in a pediatric population with tachyarrhythmias. The goal of this single\u2010dose study with administration of sotalol HCl at a dose level of 30 mg\/m<jats:sup>2<\/jats:sup> body surface area (BSA) was to define the PK of the drug in the following four age groups: neonates (0\u201330 days), infants (1 month to 2 years), younger children (&gt; 2 to &lt; 7 years), and older children (7\u201312 years) with tachyarrhythmias of either supraventricular or ventricular origin. The drug was administered in an extemporaneously compounded syrup formulation prepared from the tablets containing sotalol HCl. For safety, vital signs and adverse events were recorded and the QTc interval and heart rate telemetrically monitored. Scheduled blood samples were taken over a 36\u2010hour time interval following dose administration. The drug concentrations in plasma were measured by a sensitive and specific LC\/MS\/MS assay. Standard compartment model\u2010independent methods were applied to compute the salient PK parameters of sotalol. Twenty\u2010four clinical sites enrolled 34 patients. Thirty\u2010three had analyzable data. Sotalol was rapidly absorbed, with mean peak concentrations occurring 2 to 3 hours after administration. The elimination of sotalol was characterized by an average half\u2010life of between 7.4 and 9.2 hours in the four age groups. There existed statistically significant linear relationships between apparent total clearance (CL\/f) or apparent volume of distribution (V\u039b<jats:sub>z<\/jats:sub>\/f) after oral administration and the covariates BSA, creatinine clearance (CLcr), body weight (BW), or age. The best predictors for CL\/f were CLcr and BSA, whereas BW best predicted the V\u039b<jats:sub>z<\/jats:sub>\/f. The total area under the drug concentration\u2010time curve in the smallest children with a BSA &lt; 0.33 m<jats:sup>2<\/jats:sup> was significantly greater than that in the larger children. This finding indicated that the BSA\u2010based dose adjustment used in this study led to a larger exposure in the smallest children, whereas the exposure to the drug was similar in the larger children. The dose of 30 mg\/m2 was tolerated well. No serious drug\u2010related adverse events were reported. It can be concluded that the PK of sotalol in the pediatric patients depended only on body size, except for the neonates and smallest infants in whom the disposition of sotalol was determined by both body size and maturation of eliminatory processes.<\/jats:p>","DOI":"10.1177\/00912700122009818","type":"journal-article","created":{"date-parts":[[2003,7,19]],"date-time":"2003-07-19T09:38:13Z","timestamp":1058607493000},"page":"35-43","source":"Crossref","is-referenced-by-count":15,"title":["Single\u2010Dose Pharmacokinetics of Sotalol in a Pediatric Population with Supraventricular and\/or Ventricular Tachyarrhythmia"],"prefix":"10.1002","volume":"41","author":[{"given":"J. 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