ArticleFrontiers in pharmacology2026
Gabapentin CNS exposure and analgesic response are modulated by OCT2 genotype in patients with chronic neuropathic pain.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Gabapentin (GBP) is commonly used for chronic neuropathic pain, yet its therapeutic response varies widely across individuals. As a substrate of the organic cation transporter 2 (OCT2), encoded by the Methods: Data from two clinical studies (n = 94) were pooled, including single and multiple oral dose regimens of GBP. Population PK/PD modeling was performed using nonlinear mixed-effects modeling. Results: A two-compartment PK model with first-order absorption and linear elimination best described GBP disposition, with estimated apparent clearance (CL/F) significantly influenced by renal function (eGFR). Pain scores revealed delayed pain relief relative to peak plasma levels, requiring an effect compartment to link PK to an Imax model. The Conclusion: These findings highlight the importance of the OCT2 genotype in modulating GBP's analgesic efficacy. Incorporating transporter pharmacogenetics into PK/PD models may enhance individualized therapy for neuropathic pain, particularly in identifying poor responders who may benefit from alternative dosing or adjunct treatments.
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