Relationship between serum mono-hydroxy-carbazepine concentrations and adverse effects in patients with epilepsy on high-dose oxcarbazepine therapy.
OBJECTIVE
To investigate the relationship between the serum concentration of the mono-hydroxy-derivative (MHD) of oxcarbazepine (OXC) and adverse effects (AEs) in epileptic patients on high-dose OXC therapy.


METHODS
Forty-four consecutive patients, aged 18-65 years, with refractory epilepsy receiving OXC dosages > or = 1500 mg/day (range 1500-3300 mg/day) were assessed at an outpatient clinic. Serum MHD concentrations were determined by a specific HPLC assay in samples collected before the morning dose and 2 h after drug intake. An independent observer assessed AEs at each sampling time.


RESULTS
AEs were reported in five patients at the first sampling time, and in 26 patients at the second sampling time. Nystagmus, sedation, blurred vision, and dizziness were the most frequent AEs. MHD concentrations (means +/- S.D.) associated with AEs were 29.6 +/- 5.58 compared with 21.7 +/- 5.0 mg/L when no AEs were detected (p = 0.0001). AEs were minimized in most patients by reducing OXC dose, increasing the number of daily administrations, or both.


CONCLUSIONS
Patients with serum MHD concentrations > or = 30 mg/L are at greater risk of developing AEs. In many patients, AEs occur intermittently in relation to fluctuations in serum MHD. Monitoring MHD concentrations could help in the management of patients on high-dose OXC therapy.
Striano
Salvatore
S
Epilepsy Center, Department of Neurological Sciences, Federico II University, Naples, Italy. sstriano@libero.it
Striano
Pasquale
P
Di Nocera
Pierpaolo
P
Italiano
Domenico
D
Fasiello
Cecilia
C
Ruosi
Patrizia
P
Bilo
Leonilda
L
Pisani
Francesco
F
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078330:Oxcarbazepine
C039775:10,11-dihydro-10-hydroxycarbamazepine; D000927:Anticonvulsants; D002220:Carbamazepine; D000078330:Oxcarbazepine