title: Sulfoconjugation and renal excretion contribute to the interpatient variation of exogenous catecholamine clearance in critically ill children.
abstract: OBJECTIVE
  To delineate the contributions of sulfoconjugation, renal excretion, and patient age to the wide interpatient variability in exogenous dobutamine and dopamine plasma clearance.
  
  
  METHODS
  Simultaneous plasma free and sulfoconjugated dobutamine and/or dopamine, respective urine free catecholamine, and serum creatinine were determined on stable critically ill children receiving unchanged continuous infusions of dobutamine and/or dopamine for at least 1 hr. Free dobutamine and dopamine clearance rates were calculated.
  
  
  METHODS
  Pediatric and neonatal intensive care units in university settings.
  
  
  METHODS
  Forty-seven stable critically ill neonates and children.
  
  
  METHODS
  Continuous infusions of dobutamine and/or dopamine: nine patients received dopamine only, 27 patients received dobutamine only, and 11 patients received both simultaneously.
  
  
  RESULTS
  Fractions of plasma dobutamine and dopamine sulfoconjugated were 0.73 +/- 0.05 and 0.76 +/- 0.05, respectively. Free plasma dobutamine and dopamine clearances were 102 +/- 15 mL/kg/min and 250 +/- 38 mL/kg/min, respectively. Linear regression analyses demonstrated relationships of the fraction of plasma dobutamine and dopamine sulfoconjugated to the respective free plasma clearances (r2 = .30, p < .01, and r2 = 0.29, p < .01, respectively), and, more impressively, to the natural logarithm of the respective free plasma clearances (r2 = 0.58, p < .001, and r2 = 0.39, p < .01). Patients with serum creatinine concentrations >2 mg/dL had lower free plasma dobutamine and dopamine clearance rates than those patients with serum creatinine of <2 mg/dL (6 +/- 1 vs. 107 +/- 15 mL/kg/min for dobutamine and 40 +/- 38 vs. 270 +/- 39 mL/kg/min for dopamine, respectively, p < .05 for both by Mann-Whitney U test). No relationship was noted between free catecholamine clearance and age.
  
  
  CONCLUSIONS
  Sulfoconjugation and renal excretion are important determinants of the wide interpatient variability in plasma free dobutamine and dopamine clearance rates.
authors.affiliation: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona College of Medicine, Tucson, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Berg
authors.forename: J F
authors.initials: JF
authors.lastname: Padbury
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002395:Catecholamines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000097:blood; D003422:Critical Care; D004280:Dobutamine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine; D004298:Dopamine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000652:urine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models
chemical_list: D002395:Catecholamines; D004280:Dobutamine; D003404:Creatinine; D004298:Dopamine