Drug Interaction and Pharmacokinetic Modeling of Oxcarbazepine in Korean Patients With Epilepsy

Abstract

The serum concentration of OHC was statistically significantly correlated with the dose of OXC and negatively correlated with comedication of EIAED. Population pharmacokinetic analysis showed that the apparent clearance of OHC increased with comedication with EIAEDs.

Population pharmacokinetics modeling of oxcarbazepine to characterize drug interactions in Chinese children with epilepsy

“…The first-order conditional estimation method with the η-ε interaction option (FOCE L-B) was used throughout the model building process. Based on previous modeling performed on other studies [2,3] and exploratory graphical analysis, one-and two-compartment structural kinetic models with first-order elimination were evaluated. The best structural model was chosen based on an examination of the objective function value (OBJ, equal to the -2 log likelihood value of the data) and the visual inspection of standard goodness-of-fit plots, including the individual fits.…”

“…In the second step, demographic variables (this study included sex, age, weight, and body surface area) and comedication (CO) were tested as potential covariates for the PK parameters. Based on previous studies [2,3] , we considered CO to be a potential covariate explaining the kinetic differences. CO was included as a categorical variable [0 for OXC monotherapy; 1 for comedication with newer AEDs (NEWAEDs) such as levetiracetam (LEV), LTG and topiramate (TPM); 2 for comedication with enzymeinhibiting AEDs such as valproic acid (VPA); and 3 for comedication with enzyme-inducing AEDs (EIAEDs) such as CBZ and PB].…”

“…OXC, the 10-keto derivative of carbamazepine (CBZ), has a similar clinical efficacy as CBZ, but with fewer adverse drug reactions and better tolerability [3,4] . The oral bioavailability of OXC is above 95%.…”

“…Usually, the pharmacokinetics and disposition of the racemate were investigated [4] . A number of studies [2,3,10] have reported a linear relationship between OXC doses and MHD concentrations in patients and healthy volunteers，and MHD accounted for the majority of the radio-active species circulating in plasma, with only low levels of unchanged OXC; therefore, OXC acts as a prodrug of MHD [4] . MHD was typically the target of the pharmacokinetic or pharmacodynamic investigations of OXC.…”

“…Thus, it has been suggested that there was no relationship between concomitant administration with other AEDs and the apparent clearance of MHD [10] . However, some studies have reported a higher apparent clearance and lower MHD concentrations when OXC was coadministered with enzyme-inducing medications [1][2][3]11] . Furthermore, it has been demonstrated that OXC was a weak inhibitor of CYP2C19 and may increase the serum concentration of PHT and PB [2,5,12] .…”