Abstract
Background and Objectives
The controlled-release (CR) formulation of pregabalin is designed to remain in the stomach for a prolonged period while slowly releasing pregabalin for absorption in the small intestine. This study evaluated the effect of the gastrointestinal prokinetic agent, erythromycin, on the pharmacokinetics of a single dose of pregabalin CR 330 mg administered following an evening meal and the safety and tolerability of a single dose of pregabalin CR 330 mg when administered with and without multiple doses of erythromycin 500 mg.
Methods
This was a phase I, open-label, randomized, two-period, two-treatment crossover study. Participants received (in a randomized sequence) a single oral dose of pregabalin CR 330 mg alone and pregabalin CR 330 mg co-administered with multiple doses of erythromycin 500 mg. The CR formulation was administered immediately following a standardized 600−750 calorie 30 % fat evening meal. Erythromycin 500 mg was administered orally approximately 1 h prior to pregabalin CR, as well as 6 and 12 h following the first erythromycin dose. Blood samples were collected up to 48 h post-pregabalin CR dose. Pharmacokinetic parameters were estimated from concentration–time data using standard noncompartmental methods. Adverse events were monitored throughout.
Results
Eighteen healthy participants (aged 19−52 years) received pregabalin CR. Co-administration of pregabalin CR with erythromycin resulted in a 17 % decrease in total exposure [area under the plasma concentration–time curve from zero to infinity (AUC∞)] and a 13 % decrease in peak plasma concentrations (C max) relative to pregabalin CR administered alone. The 90 % CI for the ratio of the adjusted geometric mean AUC∞ was 76.5−89.2 % (outside the 80−125 % range prespecified for bioequivalence). Adverse events were of mild to moderate severity and the adverse event profile was similar for pregabalin CR administered with and without erythromycin.
Conclusion
Co-administration of multiple high doses of erythromycin resulted in 17 % lower pregabalin exposure for a single dose of pregabalin CR 330 mg than for pregabalin CR 330 mg administered alone. Although the two treatments did not achieve formal bioequivalence, the impact of co-administered erythromycin treatment was small and not considered clinically relevant.
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Acknowledgments
This study was sponsored by Pfizer, who were involved in the study design, the collection, analysis, and interpretation of the data, the writing of the report, and the decision to submit the paper for publication. Medical writing support was provided by Lorna Forse, PhD, and Penny Gorringe, MSc, of Engage Scientific Solutions and funded by Pfizer.
Conflict of interest
Marci L. Chew, Anna Plotka, Christine W. Alvey, Verne W. Pitman, and Joseph M. Scavone are all full-time employees of Pfizer and hold stock in Pfizer. Howard N. Bockbrader and Tanja Alebic-Kolbah were employees of Pfizer at the time this study was conducted and both hold stock in Pfizer.
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Chew, M.L., Plotka, A., Alvey, C.W. et al. Effect of the Gastrointestinal Prokinetic Agent Erythromycin on the Pharmacokinetics of Pregabalin Controlled-Release in Healthy Individuals: A Phase I, Randomized Crossover Trial. Clin Drug Investig 35, 299–305 (2015). https://doi.org/10.1007/s40261-015-0281-y
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DOI: https://doi.org/10.1007/s40261-015-0281-y