Comparative Pharmacokinetic Profiles of a Novel Low-Dose Micronized Formulation of Raloxifene 45 mg (AD-101) and the Conventional Raloxifene 60 mg in Healthy Subjects.
micronized formulation
osteoporosis
pharmacokinetics
raloxifene
safety
Journal
Clinical pharmacology in drug development
ISSN: 2160-7648
Titre abrégé: Clin Pharmacol Drug Dev
Pays: United States
ID NLM: 101572899
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
13
04
2023
accepted:
29
07
2023
medline:
4
12
2023
pubmed:
25
8
2023
entrez:
25
8
2023
Statut:
ppublish
Résumé
Raloxifene hydrochloride shows poor bioavailability (only 2%) when orally administered because of its poor aqueous solubility and its extensive first-pass metabolism. A new micronized formulation of raloxifene was developed to improve bioavailability via enhanced gastrointestinal absorption. The primary objective of this study was to evaluate the pharmacokinetic characteristics of a new micronized raloxifene formulation (AD-101) in comparison with the conventional raloxifene formulation. This study was designed as an open-label, randomized, 2-treatment-period, crossover study with a 2-week washout period. Two treatments consisted of micronized raloxifene 45 mg daily; and conventional raloxifene 60 mg daily administered in fasting conditions. Plasma raloxifene concentrations were determined by a validated method using ultra-fast liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using a noncompartmental model. In total, 49 subjects completed the study. The geometric mean ratio (micronized/conventional) of the maximum concentration and the area under the plasma concentration-time curve from time zero to the last concentration values were 1.08 (90% CI, 0.95-1.24) and 0.97 (90% CI, 0.89-1.05), respectively. The adverse event profile did not differ between the 2 formulations. The results demonstrate that micronized formulation of raloxifene 45 mg is equivalent to conventional formulation of raloxifene 60 mg when administered at the single dose in the fasted state. After single oral dosing of AD-101, there were no serious or unexpected adverse events.
Substances chimiques
Raloxifene Hydrochloride
4F86W47BR6
AD 101
0
Types de publication
Randomized Controlled Trial
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1204-1210Informations de copyright
© 2023 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.
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