10-Hydroxycarbazepine serum concentration-to-oxcarbazepine dose ratio: influence of age and concomitant antiepileptic drugs.

This study was done to evaluate the association between patient age and the concomitant use of enzyme-inducing antiepileptic drugs (AEDs) and oxcarbazepine (OXC) concentration-to-dose ratio (CDR) by a multivariate analysis. The influence of patient age and concomitant AEDs on the trough steady-state serum concentration of 10-hydroxycarbazepine (OHC) normalized to 1 mg/kg body weight of OXC or concentration-to-dose ratio (OHC-OXC-CDR) was assessed by analysis of covariance. Samples were collected from 106 patients (90% outpatients), aged 1-80, who were receiving OXC either alone (n = 41) or in combination with other AEDs (n = 65). The average OHC-OXC CDR was 0.70 +/- 0.26 (mean +/- SD). Analysis of covariance showed that patient age was influential (P < 0.001) and that there was a difference between the noninducers group (OXC or OXC + lamotrigine, topiramate, or valproate) and the inducers group (OXC + phenobarbital or phenytoin) (P < 0.001). The OHC-OXC CDR increased with age (r = 0.14, P < 0.001) and was approximately 48% lower in children aged 6 or less than in patients over 45, and approximately 32% lower in the inducers group than in patients receiving OXC alone. The correlation between OHC-OXC CDR and the age of the patients concerned with OXC alone was r = 0.48, P < 0.001. In the noninducers group the OHC-OXC CDR was 0.59 +/- 0.24 in patients aged 11 or less (n = 16), and 0.81 +/- 0.23 in patients over 11 years (n = 62). In the inducers group it was 0.25 +/- 0.11 in patients aged 11 or less (n = 3) and 0.57 +/- 0.18 in patients over the age of 11 (n = 25). The OHC-OXC CDR increased with patient age and decreased in the presence of enzyme-inducing AEDs in epileptic patients chronically treated with OXC. These influences may be clinically relevant, and, therefore, patient age and the presence of inducers should be considered in estimating either compliance or the OXC dose needed to achieve a desired OHC concentration.