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The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy.

Sindrup, Søren H. MD, Dr Med Sci; Holbech, Jakob V. MD, PhD; Bach, Flemming W. MD, Dr Med Sci; Finnerup, Nanna B. MD, Dr Med Sci; Brøsen, Kim MD, Dr Med Sci; Jensen, Troels S. MD, Dr Med Sci
Clinical Journal of Pain: Post Acceptance: March 7, 2017
doi: 10.1097/AJP.0000000000000497
Original Article: PDF Only

Objective: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased.

Methods: Data 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 0-10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography.

Results: In 47 patients pain was reduced -1.0 (95% CI -1.5:-0.6) by imipramine, -0.4 (95% CI -0.9: 0.1) by pregabalin and -1.6 (95% CI-2.1:-1.1) by combination therapy. On monotherapy, there was no difference between responders and non-responders with respect to concentrations of imipramine (mean 161 nmol/L vs. 229 nmol/L, P=0.129) and pregabalin (mean 9.8 [mu]mol/L vs. 11.7 [mu]mol/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 [mu]mol/L) neither for mono-therapy nor for combination therapy (P=0.161-0.797). Isobulographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction.

Discussion: There were no important relations between drug concentrations and efficacy, or indication of synergistic interaction between the drugs. It was not implied that treatment can be improved by measurement of drug concentration of pregabalin.

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