Serum concentrations and effects of gabapentin and vigabatrin: observations from a dose titration study.
To explore possible concentration-effect relationships, gabapentin (GBP) and vigabatrin (VGB) serum concentrations were obtained from patients participating in an add-on dose-titration trial comparing GBP and VGB in partial epilepsy. Patients randomized to GBP started on 1800 mg/d and could have their dosage increased stepwise to 2400 and 3600 mg/d if seizures persisted. Those randomised to VGB started on 1000 mg/d, and the dose could be increased to 2000 and 4000 mg/d. Blood samples were obtained at steady state, at a nonstandardized time, from 27 patients randomized to GBP and from 36 randomized to VGB. Serum samples were analyzed using high-performance liquid chromatography. The treatment effect was expressed as percentage reduction in number of seizures from baseline. In addition, patients were classified as responders (>50% reduction in number of seizures from baseline) or nonresponders. There was no significant correlation between serum concentrations of GBP and seizure reduction at the lowest dosage, 1800 mg/d (r = -0.02, P = 0.94, Spearman-rank), nor between VGB serum levels and seizure reduction at 1000 mg/d of VGB (r = -0.14, P = 0.44). The serum GBP concentrations among responders to GBP 1800 mg/d were 26 +/- 12 micro mol/L (mean +/- SD), which was not different from serum concentrations in nonresponders, 28+/-13 micro mol/L. Nor was there a difference between serum concentrations of responders and nonresponders to VGB 1000 mg/d (32 +/- 23 and 44 +/- 36 micro mol/L, respectively). Hence, with the present study design we were unable to identify specific target ranges of GBP and VGB serum concentrations.
Lindberger
Martin
M
Department of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. martin.lindberger@neuro.hs.sll.se
Luhr
Owe
O
Johannessen
Svein I
SI
Larsson
Sirkku
S
Tomson
Torbjörn
T
D000085:Acetates / Q000097:blood* / Q000627:therapeutic use*; D000588:Amines; D000927:Anticonvulsants / Q000097:blood* / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D016903:Drug Monitoring; D004828:Epilepsies, Partial / Q000097:blood / Q000188:drug therapy; D005260:Female; D000077206:Gabapentin; D006801:Humans; D008297:Male; D020888:Vigabatrin / Q000097:blood* / Q000627:therapeutic use*; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020888:Vigabatrin