Drug Interaction Studies of Pregabalin (CI-1008, PGB) in Patients with Epilepsy Maintained on Either Valproate (VA), Lamotrigine (LMG), Phenytoin (PHY), or Carbamazepine (CBZ).
Abstract number :
1.272
Submission category :
Year :
2001
Submission ID :
2949
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; J.C. Strand, PhD, Experimental Medicine, Pfizer Inc, Ann Arbor, MI; D.L. Wesche, MD PhD, Experimental Medicine, Pfizer Inc, Ann Arbor, MI; C.W. Alvey, BS, Development Operations,
RATIONALE: PGB, a novel antiepileptic drug (AED), has been studied as adjunctive therapy in patients with refractory partial seizures. Clinical pharmacokinetic studies were conducted to determine the effect of PGB on steady-state (SS) pharmacokinetics of VA, LMG, PHY, and CBZ; and the effect of these marketed AEDs on PGB pharmacokinetics.
METHODS: 5 open-label, multiple-dose studies were performed in adult patients maintained on VA, LMG, PHY, or CBZ. PGB (200 mg q8h) was added to each patient[scquote]s AED therapy. SS trough concentrations of each marketed AED were determined from plasma obtained prior to, during, and after PGB therapy. Likewise, SS PGB concentrations were determined from plasma obtained serially during the concomitant administration of PGB and the marketed AEDs. Predose SS trough AED plasma concentrations collected prior to, during, and after PGB treatment were compared using ANOVA. 90% confidence intervals were used as an aid in data interpretation. PGB pharmacokinetic parameters were determined using standard noncompartmental methods, and these parameters were compared to those observed historically in subjects without marketed AED administration for clinically meaningful differences.
RESULTS: 12 patients per marketed AED (only 10 on PHY) completed the studies. In general, PGB adjunctive therapy was well-tolerated. Marketed SS trough AED (VA, LMG, PHY, or CBZ) concentrations were unaffected by concomitant PGB administration. PGB SS pharmacokinetic parameter values following VA, LMG, PHY or CBZ concomitant therapy were, in general, similar to those observed historically in healthy subjects receiving PGB alone.
CONCLUSIONS: PGB concomitant therapy had no effect on the pharmacokinetics of VA, LMG, PHY, and CBZ. Likewise, PGB pharmacokinetics in patients maintained on VA, LMG, PHY or CBZ were similar to those observed in healthy patients. These results indicate that PGB can be added to VA, LMG, PHY, and CBZ without concern for pharmacokinetic drug-drug interactions with PGB.
Support: Supported by Pfizer Global Research and Development.
Disclosure: Salary - Pfizer Inc; Consulting - Pfizer Inc; Stock - Pfizer Inc; Honoraria - Pfizer Inc