POPULATION ANALYSIS OF THE PHARMACOKINETICS OF TIAGABINE IN PATIENTS WITH EPILEPSY

Purpose: In two open-label long-term safety studies, we determined tia gabine (TGB) pharmacokinetics in patients with epilepsy. Methods: In a ll, 2,147 plasma samples from 511 patients who participated in the stu dies were available. The total daily dose ranged from 2 mg administere d once daily to 80 mg administered in four doses. A one-compartment mo del with first-order absorption and elimination was used to fit the TG B plasma concentration-lime data, with a population pharmacokinetic ap proach. Results: The patients' average (+/-SD) weight and age were 73. 8 +/- 20.7 kg and 32.1 +/- 12.3 years. The most significantly factor a ffecting TGB pharmacokinetics was concomitant administration of other antiepileptic drugs (AEDs). The central clearance value in patients re ceiving AEDs known to induce hepatic drug metabolism was 21.4 L/h, a v alue 67% higher than the central clearance estimate obtained for the p atients receiving AEDs not known to affect hepatic drug metabolism (12 .8 L/h). Then was no evidence of any dose or time effect, indicating t hat TGB pharmacokinetics are linear. TGB pharmacokinetics were not dif ferent in white, black, or Hispanic patients, although our ability to explore racial effects was limited since 90% of the patients were whit e. No other demographic variables (including age and smoking) or any c linical chemistry measurements(including bilirubin, SGOT, and SGPT) we re important in explaining the variability in the clearance estimates. Conclusions: TGB pharmacokinetics are linear, influenced by enzyme-in ducing AEDs, and largely unaffected by other demographic variables.