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Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high‐performance liquid chromatography coupled to tandem mass spectrometry
Author(s) -
Mendes Gustavo D.,
Pereira Thais da Silva,
Rodrigues Júlio César,
Santos Elaine Marcílio,
Souza Mariani Rafaela,
LopesMartins Rodrigo Alvaro Brandão,
Antunes Natalícia de Jesus,
Moreno Ronilson Agnaldo,
De Nucci Gilberto
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4731
Subject(s) - bioequivalence , chemistry , zolpidem , bioavailability , chromatography , pharmacokinetics , confidence interval , high performance liquid chromatography , liquid chromatography–mass spectrometry , area under the curve , mass spectrometry , pharmacology , medicine , insomnia
To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration ( C max ), area under curve (AUC), half‐life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69–106.16) for C max, 97.44% (90% CI = 91.85–103.37%) for area under curve of plasma concentration until the last concentration observed (AUC last ) and 98.30% (90% CI = 92.48–104.49) for the area under curve between the first sample (pre‐dosage) and infinity (AUC 0–inf ). Since the 90% CI for AUC last , AUC 0–inf and C max ratios were within the 80–125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.