Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters

TY - JOUR

T1 - Carvedilol therapy in pediatric patients with congestive heart failure: a study investigating clinical and pharmacokinetic parameters

AU - Läer, Stephanie

AU - Mir, Thomas S

AU - Behn, Frederike

AU - Eiselt, Michele

AU - Scholz, Hasso

AU - Venzke, Andrea

AU - Meibohm, Bernd

AU - Weil, Jochen

PY - 2002/5

Y1 - 2002/5

N2 - OBJECTIVE: Our purpose was to evaluate the clinical effect of carvedilol among pediatric patients with congestive heart failure (CHF) who did not respond to standard therapy and to assess the pharmacokinetics of carvedilol among these children.METHODS: In this prospective, open intervention trial with blinded interpretation of selected end points, patients with CHF who did not improve on standard therapy, including digoxin, angiotensin-converting enzyme inhibitors, and diuretics, were treated with oral carvedilol in a ramped dosing scheme. Clinical parameters (ejection fraction, fractional shortening, and modified Ross score) were assessed before initiation of treatment and monthly for 6 months. Pharmacokinetic profiles of carvedilol were determined over the first 12-hour period after the initial dose in study patients, and for comparison, in 9 healthy adult volunteers.RESULTS: Fifteen patients (aged 6 weeks to 19 years) were enrolled in the study, including 10 patients with dilated cardiomyopathy and 5 with CHF secondary to congenital heart disease. All 15 patients tolerated carvedilol for the duration of the trial, and all achieved maximum target dosing. After 6 months of carvedilol therapy, ejection fraction increased (36% vs 54%; P <.05) and modified Ross Score improved (5 +/- 2 vs 3 +/- 3; P <.05). Elimination half-life was about 50% shorter in pediatric CHF patients compared with healthy adult volunteers (2.9 vs 5.2 hours; P <.05).CONCLUSIONS: Pediatric patients with CHF not responding to standard therapy may benefit from oral carvedilol treatment. The observed increased elimination of carvedilol in children suggests that optimal dosing strategies need to be further defined among the pediatric population.

AB - OBJECTIVE: Our purpose was to evaluate the clinical effect of carvedilol among pediatric patients with congestive heart failure (CHF) who did not respond to standard therapy and to assess the pharmacokinetics of carvedilol among these children.METHODS: In this prospective, open intervention trial with blinded interpretation of selected end points, patients with CHF who did not improve on standard therapy, including digoxin, angiotensin-converting enzyme inhibitors, and diuretics, were treated with oral carvedilol in a ramped dosing scheme. Clinical parameters (ejection fraction, fractional shortening, and modified Ross score) were assessed before initiation of treatment and monthly for 6 months. Pharmacokinetic profiles of carvedilol were determined over the first 12-hour period after the initial dose in study patients, and for comparison, in 9 healthy adult volunteers.RESULTS: Fifteen patients (aged 6 weeks to 19 years) were enrolled in the study, including 10 patients with dilated cardiomyopathy and 5 with CHF secondary to congenital heart disease. All 15 patients tolerated carvedilol for the duration of the trial, and all achieved maximum target dosing. After 6 months of carvedilol therapy, ejection fraction increased (36% vs 54%; P <.05) and modified Ross Score improved (5 +/- 2 vs 3 +/- 3; P <.05). Elimination half-life was about 50% shorter in pediatric CHF patients compared with healthy adult volunteers (2.9 vs 5.2 hours; P <.05).CONCLUSIONS: Pediatric patients with CHF not responding to standard therapy may benefit from oral carvedilol treatment. The observed increased elimination of carvedilol in children suggests that optimal dosing strategies need to be further defined among the pediatric population.

KW - Administration, Oral

KW - Adolescent

KW - Adrenergic beta-Antagonists/pharmacokinetics

KW - Adult

KW - Carbazoles/pharmacokinetics

KW - Carvedilol

KW - Child

KW - Child, Preschool

KW - Female

KW - Heart Failure/drug therapy

KW - Humans

KW - Infant

KW - Male

KW - Patient Selection

KW - Propanolamines/pharmacokinetics

KW - Prospective Studies

U2 - 10.1067/mhj.2002.121265

DO - 10.1067/mhj.2002.121265

M3 - SCORING: Journal article

C2 - 12040358

VL - 143

SP - 916

EP - 922

JO - AM HEART J

JF - AM HEART J

SN - 0002-8703

IS - 5

ER -