• Søren H Sindrup, Jakob V Holbech, Flemming W Bach, Nanna B Finnerup, Kim Brøsen, and Troels S Jensen.
• *Department of Neurology, Odense University Hospital §Clinical Pharmacology, Institute of Public Health, University of Southern Denmark, Odense Departments of †Neurology ‡Department of Neurology and Danish Pain Research Center, Aarhus University Hospital, Aarhus, Denmark.
• Clin J Pain. 2017 Dec 1; 33 (12): 1047-1052.

ObjectiveThe aim of this study was to explore the serum concentration-effect relation for first-line drugs in neuropathic pain and to determine if efficacy could be increased.MethodsData from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin, and their combination in painful polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0 to 10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography.ResultsIn 47 patients, pain was reduced -1.0 (95% confidence interval [CI], -1.5 to -0.6) by imipramine, -0.4 (95% CI, -0.9 to 0.1) by pregabalin, and -1.6 (95% CI, -2.1 to -1.1) by combination therapy. On monotherapy, there was no difference between responders and nonresponders with respect to concentrations of imipramine (mean, 161 vs. 229 nmol/L, P=0.129) and pregabalin (mean, 9.8 vs. 11.7 μmol/L, P=0.178). There was no correlation between drug concentration and pain reduction for imipramine (r=0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine < or ≥100 nmol/L, pregabalin < or ≥10 μmol/L) either for monotherapy or for combination therapy (P=0.161 to 0.797). Isobolographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction.DiscussionThere were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not concluded that treatment can be improved by measurement of drug concentration of pregabalin.

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