PMID- 10369622
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20170214
IS  - 1060-0280 (Print)
IS  - 1060-0280 (Linking)
VI  - 33
IP  - 5
DP  - 1999 May
TI  - Use of intravenous valproate in three pediatric patients with nonconvulsive or 
      convulsive status epilepticus.
PG  - 579-84
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 anticonvulsants. CASE SUMMARY: Two 
      patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, 
      phenytoin, and pentobarbital received intravenous VPA. Apparent volume of 
      distribution (Vd) 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 Vd 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 
      produce 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.
FAU - Hovinga, C A
AU  - Hovinga CA
AD  - Pediatric Pharmacotherapy, The University of Tennessee, Memphis 38163, USA.
FAU - Chicella, M F
AU  - Chicella MF
FAU - Rose, D F
AU  - Rose DF
FAU - Eades, S K
AU  - Eades SK
FAU - Dalton, J T
AU  - Dalton JT
FAU - Phelps, S J
AU  - Phelps SJ
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann Pharmacother
JT  - The Annals of pharmacotherapy
JID - 9203131
RN  - 0 (Anticonvulsants)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - I4744080IR (Pentobarbital)
SB  - IM
MH  - Anticonvulsants/administration & dosage/*pharmacokinetics
MH  - Child
MH  - Child, Preschool
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - Enzyme Induction
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Pentobarbital/pharmacokinetics
MH  - Seizures/*drug therapy
MH  - Status Epilepticus/*drug therapy
MH  - Valproic Acid/administration & dosage/*pharmacokinetics
EDAT- 1999/06/16 00:00
MHDA- 1999/06/16 00:01
CRDT- 1999/06/16 00:00
PHST- 1999/06/16 00:00 [pubmed]
PHST- 1999/06/16 00:01 [medline]
PHST- 1999/06/16 00:00 [entrez]
AID - 10.1345/aph.18349 [doi]
PST - ppublish
SO  - Ann Pharmacother. 1999 May;33(5):579-84. doi: 10.1345/aph.18349.