Population Pharmacokinetic (PK) Analyses of Commonly Prescribed Antiepileptic Drugs (AEDs) Coadministered with Pregabalin (PGB) in Adult Patients with Refractory Partial Seizures.
Abstract number :
1.264
Submission category :
Year :
2001
Submission ID :
2969
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
H.N. Bockbrader, PhD, Clinical Pharmacokinetics, Pfizer, Inc, Ann Arbor, MI; P.J. Burger, BS, Development Operations, Pfizer, Inc, Ann Arbor, MI; A.R. Kugler, PhD, Clinical Research, Pfizer, Inc, Ann Arbor, MI; L.E. Knapp, PharmD, Clinical Research, Pfize
RATIONALE: PGB, a novel antiepileptic drug (AED), has been studied as adjunctive therapy in patients with refractory partial seizures. The purpose of these meta-analyses is to investigate the possible effect of concomitant PGB administration on the population PKs of commonly prescribed AEDs in patients with partial seizures.
METHODS: Refractory patients (N[gte]40 per AED) with partial seizures maintained on carbamazepine (CBZ), lamotrigine (LMG), phenobarbital (PB), phenytoin (PHT), tiagabine (TGB), topiramate (TPM), or valproate (VPA) therapy and who participated in 3 PGB add-on trials were included in the analyses. Baseline and double-blind steady-state (SS) plasma AED concentration-time data (sparse sampling), AED daily dose, and double-blind treatment (placebo/PGB) were used in the analyses. Data were modeled using NONMEM (1-compartment open model with instantaneous absorption) to estimate population PK parameters (mean and intersubject variability) of each AED during baseline and double-blind phases. 90% confidence intervals (CI) were used to determine if concomitant PGB or placebo administration had an effect on each AED[scquote]s clearance.
RESULTS: SS plasma concentrations for all AEDs during baseline (without PGB) and double-blind phases with PGB were similar. The 90% CI for CBZ (N=540), LMG (N=198), PB (N=47), PHT (N=267), TPM (N=142), and VPA (N=189) CL were all within the 80-125% range indicating that concomitant PGB administration had no important effect on the CL of these AEDs. Interpretation of the TGB data was less straightforward as both PGB and placebo treatments increased TGB CL. The change in TGB CL for both treatments was not statistically significant; however, no conclusion can be drawn due to the uncertainty (wider 90% CI) observed in the data.
CONCLUSIONS: Pregabalin has no clinically significant effect on the steady-state pharmacokinetics of CBZ, LMG, PB, PHT, TPM, or VPA. Thus, pregabalin can be coadministered with these commonly prescribed AEDs without concern for clinically significant changes in their pharmacokinetics.
Support: Pfizer Global Research and Development
Disclosure: Salary - Pfizer, Inc Stock - Pfizer, Inc