In:
Therapeutic Drug Monitoring, Ovid Technologies (Wolters Kluwer Health), Vol. 39, No. 2 ( 2017-04), p. 118-123
Abstract:
A monocentric, single-dose, open-label, 2-way, crossover randomized study was conducted by the San Matteo Phase I Clinical Trial Unit and Experimental Therapy (Pavia, Italy) to assess the bioequivalence and the systemic tolerability of a new oral formulation of levosulpiride (tablet 25 mg: test) versus a commercially available formulation on the Italian market (tablet 25 mg: reference). Methods: Thirty-five healthy adult volunteers, men (n = 19) and women (n = 16), aged between 18 and 55 years were screened and 32 of them were enrolled in the study. After having signed the written informed consent, each subject received a single oral dose of Test or Reference product with 250 mL of natural mineral water, in fasting conditions, interspersed with a 6-day washout period Blood samples were collected up to 36 hours after drug administration: the drug plasma levels were determined by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. The pharmacokinetic parameters included peak plasma concentration (C max ), time corresponding to C max (t max ), area under the plasma concentration–time curve from zero to infinity (AUC 0 –∞ ) or to the last sampling time assessment (AUC 0–36 ), the elimination rate constant (ke), and the terminal half-life (t 1/2 ). Safety was measured by pre- and post-treatment specific biochemical investigations, physical examination, electrocardiogram, occurrence of adverse events, and any information on patients' withdrawal. Results: The geometric mean ratio Test/Reference (90% confidence interval) for levosulpiride was 103.0% (95.8–110.8) for AUC 0–36 , 103.6% (95.9–111.9) for AUC 0–∞ , and 104.3% (94.9–114.6) for C max . ke and t 1/2 were 0.07 (SD: 0.02) and 9 hours (8–12) for both the formulations. Clearance (L/h) was 29.6 (±13.5) and 30.7 (±14.2) for the test and the reference product, respectively. Conclusions: Because the acceptance criteria required by the drug regulatory agency (European Medicines Agency, EMA) for bioequivalence prescribe limits of 80%–120% for untransformed data and 80%–125% for “ ln ” transformed data, we can confirm that the 2 formulations are bioequivalent, in terms of the rate and extent of absorption.
Type of Medium:
Online Resource
ISSN:
0163-4356
DOI:
10.1097/FTD.0000000000000380
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2048919-5
SSG:
15,3
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