title: Digoxin concentration in saliva and plasma in infants, children, and adolescents with heart disease.
abstract: BACKGROUND
  Because of its narrow therapeutic index, therapeutic monitoring of digoxin is important in the management of infants and children receiving the drug for cardiac failure or arrhythmias, or following accidental ingestion. Whether saliva can replace plasma in the therapeutic monitoring of digoxin therapy in children is unclear.
  
  
  OBJECTIVE
  This study assessed the value of determining saliva digoxin concentration in infants, children, and adolescents.
  
  
  METHODS
  Infants, children, and adolescents receiving digoxin for various indications, whose digoxin dosage had remained unchanged for ≥10 days, and whose compliance was good according to the parents were enrolled. Digoxin concentration was measured in paired specimens of citric acid-stimulated mixed saliva and plasma obtained simultaneously.
  
  
  RESULTS
  Eighteen children (10 boys, 8 girls; mean [SD] age, 42.3 [53.1] months [range, 2 months-14 years]) were included in the study. Digoxin therapy was administered for cardiac failure due to dilated cardiomyopathy in 9 patients (50.0%), ventricular septal defect in 4 (22.2%), supraventricular tachycardia in 3 (16.7%), and after cardiac surgery in 2 (11.1%). Digoxin concentration in the 20 paired specimens obtained varied from 0.0 to 0.92 ng/mL (mean [SD], 0.25 [0.26] ng/mL) in saliva and from 0.27 to 1.54 ng/mL (mean [SD], 0.77 [0.40] ng/mL) in plasma. The mean plasma/saliva digoxin concentration ratio was 2.8.
  
  
  CONCLUSIONS
  This study of infants, children, and adolescents receiving digoxin for a variety of indications and whose dose was unchanged for ≥10 days showed that marked individual variability in the saliva/plasma concentration ratio precludes the use of saliva in predicting the plasma digoxin concentration. The value of saliva digoxin (as opposed to plasma digoxin) measurements in the assessment of the cardiac effects of the drug in children remains to be determined.
authors.affiliation: Pediatric Cardiology Unit, Division of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Zalzstein
authors.affiliation: Pediatric Cardiology Unit, Division of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Nili
authors.initials: N
authors.lastname: Zucker
authors.affiliation: Pediatric Cardiology Unit, Division of Pediatrics, Soroka University Medical Center, Beer-Sheva, Israel, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Matityhau
authors.initials: M
authors.lastname: Lifshitz
keywords: digoxin; drug monitoring; plasma; saliva