Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data

Abstract

The current models, which describe CL of CBZ and CBZE in terms of patient specific details, can be used as a reference to optimize CBZ therapy in Chinese epilepsy patients.

Population pharmacokinetic of antiepileptic drugs in different populations

“…Although some authors reported nonlinear influence of total daily dose on CBZ clearance [24,29,30], our findings have shown that the relationship was linear. That is in agreement with results from the studies carried out in children, adolescents and adults [27,34].…”

“…Phenobarbital is a very potent inducer CYP3A4, CYP2C8 and CYP1A2 isoenzymes that are active participate in metabolism of CBZ. As demonstrated in previous studies, the effect concomitant therapy PB with CBZ led to significant increase in CBZ clearance and it is very important for clinical practice in the treatment of epilepsy [27,[29][30][31]33]. …”

“…In our study was measured total (bound and unbound) CBZ concentration and has been noted slight increase on CBZ clearance which could be caused by displacement from plasma protein in presence concomitant therapy with VPA. Consequently, clearance of CBZ was increased by 7% in Japanese population and by 23% in the population of Chinese children when VPA was introduced [29,30], but Delgado and Gray did not observe effect of VPA in their studies [27,31]. Treatment of pediatric and adult patients with carbamazepine could be complicated due to various factors influenced on its disposition.…”

The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation

“…This study aimed to investigate the effect of delayed or missed CBZ doses on the pharmacokinetics of CBZ and CBZE and provide practical recommendations for the patients and clinicians by using a Monte Carlo simulation, according to our previous population pharmacokinetic study in Chinese epilepsy patients [14] .…”

Population Pharmacokinetic Analysis of Therapeutic Drug Monitoring Data in Optimizing Pharmacotherapy of Antiepileptic Drugs

“…For that reason Vd is usually not estimated in population analysis of TDM data. Moreover, insufficient sampling during the absorption phase of per os given drugs, does not allow estimation of the parameters of the absorption process (rate constant of absorption); hence its values should be fixed to the literature value (Booth & Gobburu, 2003;Jiao et al, 2004;Wade et al, 1993). It has been shown (Wade et al, 1993) when no data were available from the absorption phase, misspecification of rate constant of absorption had no effect on other estimated parameters of the model.…”