Clinical utility of a continuous intravenous infusion of valproic acid in pediatric patients.
OBJECTIVE
To describe the dose-concentration relationship of a continuous intravenous infusion of valproic acid (VPA) in pediatric patients when a dosing protocol is used.


METHODS
Retrospective and concurrent chart review.


METHODS
Tertiary care, 473-bed, academic medical center with a 120-bed, dedicated children's hospital.


METHODS
Twenty-six pediatric patients (< 18 yrs old) who received VPA according to the protocol for continuous intravenous infusions between January 1, 2004, and March 31, 2006, identified by using a pharmacy order-entry system.


RESULTS
Patient demographics, VPA treatment regimens, clinical responses, and safety data were recorded and analyzed. Median patient age was 8.5 years (range 1.4-16 yrs). Approximately two thirds received VPA for seizures, and one third for migraines. Patients were given a mean +/- SD VPA loading dose of 28.5 +/- 5.2 mg/kg followed by a continuous infusion rate of 1 +/- 0.2 mg/kg/hour. Mean +/- SD serum concentration measured 4.5 +/- 1.6 hours after the loading dose was 83.3 +/- 22.8 microg/ml. Steady-state concentration at 23.3 +/- 3.0 hours after the start of the continuous infusion was 80.0 +/- 26.0 microg/ml. Postload and steady-state serum concentrations were within the target concentration of 50-100 microg/ml in 77% and 69% of patients, respectively. On further analysis, when the target range was expanded to 50-125 microg/ml (125 microg/ml was deemed acceptable if no adverse effects were noted), 89% and 92% of patients, respectively, had postload and steady-state VPA serum concentrations within this range. The response rate was excellent, with nearly 85% of patients achieving a complete or partial response to therapy. Adverse effects were generally mild and uncommon.


CONCLUSIONS
The continuous-infusion protocol permitted rapid intravenous loading of VPA in pediatric patients while minimizing adverse events and achieving concentrations in the upper region of the therapeutic range.
Taylor
Lisa M
LM
Department of Pharmacy Services, Shands Hospital at the University of Florida, Florida, USA.
Farzam
Farjam
F
Cook
Aaron M
AM
Lewis
Daniel A
DA
Baumann
Robert J
RJ
Kuhn
Robert J
RJ
D000284:Administration, Oral; D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D017723:Drug Utilization Review / Q000706:statistics & numerical data*; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006212:Hallucinations / Q000139:chemically induced; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008499:Medical Records / Q000706:statistics & numerical data*; D008657:Metabolic Clearance Rate; D008881:Migraine Disorders / Q000175:diagnosis / Q000188:drug therapy; D010634:Phenobarbital / Q000008:administration & dosage / Q000627:therapeutic use; D010672:Phenytoin / Q000008:administration & dosage / Q000627:therapeutic use; D012189:Retrospective Studies; D012640:Seizures / Q000175:diagnosis / Q000188:drug therapy; D000077236:Topiramate; D016896:Treatment Outcome; D014635:Valproic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital