Comparative Bioavailability of Metformin Hydrochloride Oral Solution Versus Metformin Hydrochloride Tablets in Fasting Mexican Healthy Volunteers.

Autor: Garza-Ocañas L; Pharmacology and Toxicology Department From Meidicine Faculty, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico., González-Canudas J; Research and Development Department, Laboratorios Silanes, S.A. de C.V., Mexico City, Mexico. jogonzalez@silanes.com.mx.; Internal Medicine Department, IMSS-Centro Médico Nacional Siglo XXI, Mexico City, Mexico. jogonzalez@silanes.com.mx., Tamez-de la O E; Pharmacology and Toxicology Department From Meidicine Faculty, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico., Badillo-Castañeda C; Pharmacology and Toxicology Department From Meidicine Faculty, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico., Gómez-Meza MV; Faculty of Economics, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico., Romero-Antonio Y; Research and Development Department, Laboratorios Silanes, S.A. de C.V., Mexico City, Mexico., Molina-Pérez A; Research and Development Department, Laboratorios Silanes, S.A. de C.V., Mexico City, Mexico., Amador-Hernández AG; Research and Development Department, Laboratorios Silanes, S.A. de C.V., Mexico City, Mexico.
Jazyk: angličtina
Zdroj: Advances in therapy [Adv Ther] 2019 Feb; Vol. 36 (2), pp. 407-415. Date of Electronic Publication: 2018 Dec 18.
DOI: 10.1007/s12325-018-0853-3
Abstrakt: Introduction: Metformin tablets may be challenging to swallow not only for those patients with dysphagia but also for children and the elderly. A metformin solution was developed for easier administration and flexible dose adjustment mantained with the same bioavailability of tablets. The objective of this study was to assess the single-dose oral bioavailability of metformin hydrochloride administered as an oral solution (500 mg/5 mL) compared with metformin hydrochloride 500 mg tablets in fasting Mexican healthy volunteers.
Methods: A randomized, single dose, two-period, two-sequence, crossover study design with a 7-day washout interval was conducted. Subjects were randomly assigned to receive a single dose of 500 mg metformin hydrochloride, either as an oral solution (test drug) or as a tablet (reference drug), after 10 h of fasting. Plasma samples (16) were collected over a 16-h period after drug administration. Bioequivalence was declared when the ratio for the 90% confidence intervals (CI) of the difference in the means of the log-transformed area under the concentration-time curve from time 0 to the last observed concentration time (AUC 0-t ), the area under the concentration-time curve extrapolated to infinite time (AUC 0-∞ ), and the maximum plasma concentration (C max ) of the two products were within 0.80 and 1.25 interval. Plasma concentrations were analyzed using reverse phase chromatography by tandem mass spectrometry (LC-MS/MS). Safety and tolerability of metformin were also assessed in all subjects.
Results: 24 subjects were enrolled and completed the study (15 female and 9 male). Test and reference metformin hydrochloride were bioequivalent during the extent of exposure since AUC 0-t and C max 90% CIs corresponded to 89.77-101.08% and 89.63-102.48%, respectively, both being within the pre-specified acceptance range criteria (80-125%). There were two adverse events (AE) with the reference formulation that were not related to the study drug.
Conclusions: Bioequivalence in healthy volunteers in fasting conditions of the two metformin hydrochloride formulations (oral solution and tablets) was established, being the difference in means of AUC 0-t , AUC 0-∞ and C max within the acceptance range (80-125%). Oral solution formulation could offer the advantages of allowing adjusted doses and easier swallowing for every patient. Plain language summary is available for this article.
Trial Registration: National Clinical Trials Registry (RNEC by its Spanish acronym), BD METF-Sil No. 86-15. Mexican Medicine Agency (COFEPRIS) Registry: 153300410B0368.
Funding: Laboratorios Silanes, S.A. de C.V.
Databáze: MEDLINE
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