Poor applicability of estimation method for adults to calculate unbound serum concentrations of valproic acid in epileptic neonates and infants.
OBJECTIVE
To characterize the relationship between total and unbound concentrations of valproic acid (VPA) in epileptic neonates and infants, the clinical examination records of those patients archived via therapeutic drug monitoring (TDM) activities were retrospectively analyzed.


METHODS
The screening encompassed 249 records of 114 epileptic patients aged 0-19 years old, who were treated with VPA monotherapy and whose total and unbound VPA concentrations were determined. These data were divided into groups according to the patients' age. In each group, the relationship between total and unbound VPA concentrations was compared to a reference profile, and the deviation from the reference was evaluated. The reference profile was calculated using the Langmuir equation, in which two parameters Kd and Bm were set to 7.8 and 130 microg/mL, respectively, according to our previous findings.


RESULTS
The relationship between total and unbound VPA concentrations of patients of 0 years old considerably deviated from the reference, and their unbound VPA concentrations were generally higher compared to the corresponding reference values. It is suggested that the large deviation is related to the fact that the serum albumin concentrations of patients younger than 1 year old tend to be lower than those of patients in other age groups.


CONCLUSIONS
Since the relationship between the VPA concentrations of epileptic neonates and infants is noticeably different from the reference, the unbound serum VPA concentrations of these patients are not adequately estimated using the same method as that for grown-ups. The unbound VPA concentrations of neonates and infants should be explicitly determined via TDM activities.
Ueshima
S
S
Department of Hospital Pharmacy, Okayama University Hospital, Okayama, Japan.
Aiba
T
T
Ishikawa
N
N
Sato
T
T
Kawasaki
H
H
Kurosaki
Y
Y
Ohtsuka
Y
Y
Sendo
T
T
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D016903:Drug Monitoring / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011485:Protein Binding; D012016:Reference Values; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D014635:Valproic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
D000927:Anticonvulsants; D012709:Serum Albumin; D014635:Valproic Acid