Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus

Collin A. Hovinga, Mike F. Chicella, Doug F. Rose, Shannan K. Eades, James T. Dalton, Stephanie Phelps

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

OBJECTIVE: To report the pharmacokinetics of intravenous valproate (VPA) in children with generalized convulsive status epilepticus (GCSE) or nonconvulsive status epilepticus (NCSE). To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsant. CASE SUMMARY: Two patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, phenytoin, and pentobarbital received intravenous VPA. Apparent volume of distribution (V(d)) following a 20 mg/kg loading dose was 0.29 L/kg. Maintenance infusions of 4-6 mg/kg/h produced steady-state total concentrations of 66 mg/L and 92.4 mg/L (unbound concentration 44.6 mg/L). Clearance ranged from 63-66 mL/h/kg. An eight- year-old with NCSE received intravenous VPA (13.4 mg/kg load followed by 9 mg/kg every 8 h). Total and unbound steady-state VPA concentrations were 32.9 mg/L and 21.2 mg/L, respectively. Elimination half-life was eight hours. DISCUSSION: We constructed a pharmacokinetic simulation using VPA parameters from children receiving mono- or polyanticonvulsants. Our V(d) and elimination half-life rates were comparable with published pediatric values. Patients on hepatic inducers had clearance rates 2.5 times those of children receiving oral anticonvulsant polytherapy. Unbound fractions (48.3% and 66%) were significantly higher than normal. CONCLUSIONS: A 20 mg/kg loading dose should produced a concentration after the bolus dose of approximately 75 mg/L. Initial infusion should consider hepatic induction (noninduced = 1 mg/kg/h, polyanticonvulsant therapy = 2 mg/kg/h, and high-dose pentobarbital = 4 mg/kg/h). Adjustments should be based on response and serum concentrations.

Original languageEnglish (US)
Pages (from-to)579-584
Number of pages6
JournalAnnals of Pharmacotherapy
Volume33
Issue number5
DOIs
StatePublished - Jun 10 1999

Fingerprint

Status Epilepticus
Valproic Acid
Pediatrics
Pentobarbital
Anticonvulsants
Half-Life
Liver
Pharmacokinetics
Maintenance
Phenytoin
Phenobarbital
Benzodiazepines
Serum

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus. / Hovinga, Collin A.; Chicella, Mike F.; Rose, Doug F.; Eades, Shannan K.; Dalton, James T.; Phelps, Stephanie.

In: Annals of Pharmacotherapy, Vol. 33, No. 5, 10.06.1999, p. 579-584.

Research output: Contribution to journalArticle

Hovinga, Collin A. ; Chicella, Mike F. ; Rose, Doug F. ; Eades, Shannan K. ; Dalton, James T. ; Phelps, Stephanie. / Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus. In: Annals of Pharmacotherapy. 1999 ; Vol. 33, No. 5. pp. 579-584.
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abstract = "OBJECTIVE: To report the pharmacokinetics of intravenous valproate (VPA) in children with generalized convulsive status epilepticus (GCSE) or nonconvulsive status epilepticus (NCSE). To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsant. CASE SUMMARY: Two patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, phenytoin, and pentobarbital received intravenous VPA. Apparent volume of distribution (V(d)) following a 20 mg/kg loading dose was 0.29 L/kg. Maintenance infusions of 4-6 mg/kg/h produced steady-state total concentrations of 66 mg/L and 92.4 mg/L (unbound concentration 44.6 mg/L). Clearance ranged from 63-66 mL/h/kg. An eight- year-old with NCSE received intravenous VPA (13.4 mg/kg load followed by 9 mg/kg every 8 h). Total and unbound steady-state VPA concentrations were 32.9 mg/L and 21.2 mg/L, respectively. Elimination half-life was eight hours. DISCUSSION: We constructed a pharmacokinetic simulation using VPA parameters from children receiving mono- or polyanticonvulsants. Our V(d) and elimination half-life rates were comparable with published pediatric values. Patients on hepatic inducers had clearance rates 2.5 times those of children receiving oral anticonvulsant polytherapy. Unbound fractions (48.3{\%} and 66{\%}) were significantly higher than normal. CONCLUSIONS: A 20 mg/kg loading dose should produced a concentration after the bolus dose of approximately 75 mg/L. Initial infusion should consider hepatic induction (noninduced = 1 mg/kg/h, polyanticonvulsant therapy = 2 mg/kg/h, and high-dose pentobarbital = 4 mg/kg/h). Adjustments should be based on response and serum concentrations.",
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T1 - Use of intravenous valproate in three pediatric patients with nonconvulsive or convulsive status epilepticus

AU - Hovinga, Collin A.

AU - Chicella, Mike F.

AU - Rose, Doug F.

AU - Eades, Shannan K.

AU - Dalton, James T.

AU - Phelps, Stephanie

PY - 1999/6/10

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AB - OBJECTIVE: To report the pharmacokinetics of intravenous valproate (VPA) in children with generalized convulsive status epilepticus (GCSE) or nonconvulsive status epilepticus (NCSE). To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsant. CASE SUMMARY: Two patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, phenytoin, and pentobarbital received intravenous VPA. Apparent volume of distribution (V(d)) following a 20 mg/kg loading dose was 0.29 L/kg. Maintenance infusions of 4-6 mg/kg/h produced steady-state total concentrations of 66 mg/L and 92.4 mg/L (unbound concentration 44.6 mg/L). Clearance ranged from 63-66 mL/h/kg. An eight- year-old with NCSE received intravenous VPA (13.4 mg/kg load followed by 9 mg/kg every 8 h). Total and unbound steady-state VPA concentrations were 32.9 mg/L and 21.2 mg/L, respectively. Elimination half-life was eight hours. DISCUSSION: We constructed a pharmacokinetic simulation using VPA parameters from children receiving mono- or polyanticonvulsants. Our V(d) and elimination half-life rates were comparable with published pediatric values. Patients on hepatic inducers had clearance rates 2.5 times those of children receiving oral anticonvulsant polytherapy. Unbound fractions (48.3% and 66%) were significantly higher than normal. CONCLUSIONS: A 20 mg/kg loading dose should produced a concentration after the bolus dose of approximately 75 mg/L. Initial infusion should consider hepatic induction (noninduced = 1 mg/kg/h, polyanticonvulsant therapy = 2 mg/kg/h, and high-dose pentobarbital = 4 mg/kg/h). Adjustments should be based on response and serum concentrations.

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