Pregabalin Dosing and Serum Levels
Abstract number :
2.225
Submission category :
Antiepileptic Drugs-All Ages
Year :
2006
Submission ID :
6664
Source :
www.aesnet.org
Presentation date :
12/1/2006 12:00:00 AM
Published date :
Nov 30, 2006, 06:00 AM
Authors :
Patricia E. Penovich, Deanna L. Dickens, Jason S. Doescher, Michael D. Frost, El-Hadi Mouderres, and Frank J. Ritter
Conventional use of AEDs in the treatment of epilepsy has utilized serum levels as an indicator of appropriate daily dosage. Pregabalin (PGB), a GABA analog which binds at the [alpha][sub]2[delta][/sub] subunit of voltage gated calcium receptors, has a dose response correlation for seizure reduction in phase three human studies at the two doses studied. No serum level to dose correlation has been reported. We have evaluated the effect of daily and weight-based doses on serum levels in clinical use., Patients received PGB as adjunctive therapy for refractory partial seizures with or without secondary generalization. Doses were empirically chosen and increased for efficacy or until side effects were experienced. Serum levels were obtained at trough if possible. Serum determinations were sent to MedTox Laboratories (St Paul, MN) for determination by HPLC. Serum levels, age, weight, daily dose, mg/kg/day dose, creatinine, efficacy and reported adverse events were evaluated by retrospective chart review., Thirty-two patients ages 4-78 ( mean 33.6 [plusmn] 17.6, median 31 ) received PGB for two days to over seven years. Weights were 27.5 [ndash] 188.5 kg ( mean 68.3 [plusmn] 30.1, median 67 ). Total daily doses were 25 [ndash] 1050 mg (mean 349 [plusmn] 212, median 300 ) resulting in 0.35-10.9 mg/kg/day (mean 5.1 [plusmn] 3.1, median 4.7 ). Serum levels were 0.99 [ndash] 13.4 [mu]g/ml (mean 4.2 [plusmn] 3.1, median 4.0). There was a significant correlation p[lt] .01 for the relationship of mg/kg/day to serum concentration.
AEs reported in 11 (33%) were tiredness, weight gain, and temporary leg swelling at levels of 1-7 [mu]g/ml. Improved seizure control was reported in 56%; 1 was worse. Efficacy was seen in 7/18 at 2 [mu]g/ml or less and in 11/18 at 4-10 [mu]g/ml. Seven patients had 2 or more levels at different doses and showed linear increase in serum level., PGB is easily utilized as adjunctive therapy in clinical practice. Doses are well tolerated up to 1050 mg/day without serious AEs. Serum levels correlate linearly with increased dosing.,
Antiepileptic Drugs