Single-dose pharmacokinetics of sotalol in a pediatric population with supraventricular and/or ventricular tachyarrhythmia

The pharmacokinetics (PK) of the antiarrhythmic sotalol, which elicits Clas s ill and beta-blocking activity, has not been adequately defined in a pedi atric population with tachyarrhythmias, The goal of this single-dose study with administration of sotalol HCl at a dose level of 30 mg/m(2) body surfa ce area (BSA) was to define the PK of the drug in the following four age gr oups: neonates (0-30 days), infants (1 month to 2 years), younger children (> 2 to < 7 years), and older children (7-12 years) with tachyarrhythmias o f either supraventricular or ventricular origin. The drug was administered in an extemporaneously compounded syrup formulation prepared from the table ts containing sotalol HCl. For safety, vital signs and adverse events were recorded and the QTc interval and heart rate telemetrically monitored. Sche duled blood samples were taken over a 36-hour time interval following dose administration. The drug concentrations in plasma were measured by a sensit ive and specific LC/MS/MS assay. Standard compartment model-independent met hods were applied to compute the salient PK parameters of sotalol. Twenty-f our clinical sites enrolled 34 patients. Thirty-three 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-life of between 7.4 and 9.2 hours in the four age groups . There existed statistically significant linear relationships between appa rent total clearance (CL/f) or apparent volume of distribution (V<lambda>(z )/f) after oral administration and the covariates BSA, creatinine clearance (CLcr), body weight (BW), or age. The best predictors for CL/f were CLcr a nd BSA, whereas BW best predicted the V lambda (z/)f. The fetal area under the drug concentration-time curve in the smallest children with a BSA < 0.3 3 m(2) was significantly greater than that in the larger children. This fin ding indicated that the BSA-based dose adjustment used in this study led to a larger exposure in the smallest children, whereas the exposure to the dr ug was similar in the larger children. The dose of 30 mg/m2 was tolerated w ell. No serious drug-related adverse events were reported. It can be conclu ded 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 p rocesses. Journal of Clinical Pharmacology, 2001;41:35-43 (C) 2001 the Amer ican College of Clinical Pharmacology.