ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1692519
This article is part of the Research TopicAdvances in Novel Pharmacotherapeutics and Drug Discovery: Computational, Experimental, Translational, and Clinical Models, Volume IIView all 4 articles
Pharmacokinetics and Safety of a Fixed-Dose Combination of Pregabalin and Thioctic Acid in Healthy Volunteers: A Randomized, Open-Label, Phase 1 Crossover Study
Provisionally accepted
- 1Psicofarma SA de CV, Mexico City, Mexico
- 2Instituto Nacional de Rehabilitacion Luis Guillermo Ibarra Ibarra, Mexico City, Mexico
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Background: Pregabalin (PGB) is a first-line therapy for painful diabetic neuropathy (PDN), but its adverse effects limit use. Thioctic acid, also known as α-lipoic acid (ALA), exhibits antioxidant and neuroprotective properties. The pharmacokinetic interaction profile of their combination in humans remains incompletely characterized. Methods: In this randomized, open-label, three-period, six-sequence, single-dose crossover study, 24 healthy adults (12 males, 12 females) received PGB (80 mg), ALA (400 mg), or their fixed-dose combination under fasting conditions, with 7-day washouts. Plasma concentrations were measured at 17 time points over 36 hours using a validated UPLC–MS/MS method. Non-compartmental analysis was used to derive pharmacokinetic parameters (Cmax, tmax, AUClast, AUCinf, t½). Bioequivalence was assessed using geometric mean ratios (GMRs) and 90% confidence intervals (CIs). Results: For PGB, the GMRs (90% CIs) for Cmax and AUClast were 91.2% (82.5–100.8%) and 90.4% (80.9–100.9%), respectively. For ALA, the GMRs were 108.9% (90.6–130.8%) for Cmax and 96.5% (87.7–106.3%) for AUClast. All 90% CIs were within predefined bioequivalence ranges (80–125% for PGB and ALA AUClast, 75–133% for ALA Cmax). Adverse events were mild, transient, and resolved without intervention; no serious adverse events occurred. Conclusion: In this single-dose, Phase 1 trial in healthy volunteers, co-administration of PGB and ALA did not result in clinically significant pharmacokinetic interactions and was well tolerated. These findings provide preliminary pharmacokinetic evidence to support further clinical evaluation in patients with PDN.
Keywords: pregabalin, alpha-lipoic acid, Diabetic neuropathy, pharmacokinetics, fixed-dosecombination, Phase 1 trial, UPLC-MS/MS, Bioequivalence
Received: 25 Aug 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Zárate, Bravo-Lamicq, Ocampo-Gutiérrez de Velasco and Arias-Carrión. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Edith Zárate, edith.zarate@psicofarma.com.mx
Oscar Arias-Carrión, ariasemc2@gmail.com
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