TY - JOUR
T1 - The influence of polytherapy on the relationships between serum carbamazepine and its metabolites in epileptic children
AU - Hua, Liu
AU - Delgado, Mauricio R.
N1 - Funding Information:
This study was supported by the Research Committee of Texas Scottish Rite Hospital for Children. We wish to thank Dr. Richard Browne for his assistancei n the statistical analysis and Mr. Ronnie Houston for his help in manuscript preparation.
PY - 1994/3
Y1 - 1994/3
N2 - The influence of polytherapy on the relationships between the age, weight, carbamazepine (CBZ) dose, total clearance and intrinsic clearance, with concentrations, concentration ratios and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,1 l-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) are investigated. Three groups of patients with CBZ monotherapy, or receiving CBZ polytherapy by taking CBZ and valproic acid (VPA) or CBZ plus other antiepileptic drugs (AEDs) were studied. The significant correlations between serum CBZ concentrations and CBZ dose in patients taking CBZ alone were no longer significant in patients with polytherapy and the positive associations between serum CBZ-E concentrations and CBZ dose were lost in patients with CBZ + VPA. Only the concentrations of CBZ-H had significant correlations with CBZ dose in all three groups of patients. Results from this relationship study indicate a heteroinduction effect of other AEDs on CBZ metabolism and a relatively weak influence on CBZ-E elimination. Data also suggest that there is a block in the biotransformation from CBZ-E to CBZ-H in patients taking CBZ + VPA, presumably caused by the inhibition effect of VPA on epoxide hydrolase. Therapeutic drug monitoring of CBZ will benefit from the knowledge obtained from the relationship study.
AB - The influence of polytherapy on the relationships between the age, weight, carbamazepine (CBZ) dose, total clearance and intrinsic clearance, with concentrations, concentration ratios and level/dose ratios of CBZ, carbamazepine-10,11-epoxide (CBZ-E) and trans-10,1 l-dihydroxy-10,11-dihydro-carbamazepine (CBZ-H) are investigated. Three groups of patients with CBZ monotherapy, or receiving CBZ polytherapy by taking CBZ and valproic acid (VPA) or CBZ plus other antiepileptic drugs (AEDs) were studied. The significant correlations between serum CBZ concentrations and CBZ dose in patients taking CBZ alone were no longer significant in patients with polytherapy and the positive associations between serum CBZ-E concentrations and CBZ dose were lost in patients with CBZ + VPA. Only the concentrations of CBZ-H had significant correlations with CBZ dose in all three groups of patients. Results from this relationship study indicate a heteroinduction effect of other AEDs on CBZ metabolism and a relatively weak influence on CBZ-E elimination. Data also suggest that there is a block in the biotransformation from CBZ-E to CBZ-H in patients taking CBZ + VPA, presumably caused by the inhibition effect of VPA on epoxide hydrolase. Therapeutic drug monitoring of CBZ will benefit from the knowledge obtained from the relationship study.
KW - Antiepileptic drugs
KW - Carbamazepine
KW - Carbamazepine diol
KW - Carbamazepine epoxide
KW - Epileptic children
KW - Valproic acid
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U2 - 10.1016/0920-1211(94)90056-6
DO - 10.1016/0920-1211(94)90056-6
M3 - Article
C2 - 8013448
AN - SCOPUS:0028205074
SN - 0920-1211
VL - 17
SP - 257
EP - 269
JO - Epilepsy Research
JF - Epilepsy Research
IS - 3
ER -