Artikel ; Online: Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.
Journal of clinical psychopharmacology
2023 Band 43, Heft 4, Seite(n) 350–360
Abstract: Purpose/background: Once-daily extended-release (ER) lorazepam was developed to reduce fluctuations in plasma levels compared with lorazepam immediate-release (IR) for short-term anxiety relief. Here we report a series of phase 1 randomized, open-label, ...
Abstract | Purpose/background: Once-daily extended-release (ER) lorazepam was developed to reduce fluctuations in plasma levels compared with lorazepam immediate-release (IR) for short-term anxiety relief. Here we report a series of phase 1 randomized, open-label, multiperiod crossover studies characterizing ER lorazepam pharmacokinetics and safety in healthy adults. Methods/procedures: These phase 1 studies assessed the pharmacokinetics of ER lorazepam administered: (study 1) 3 mg once daily versus IR lorazepam 1 mg 3 times a day (TID; every 8 hours), (study 2) with or without food, and (study 3) intact versus sprinkled onto food. Study 3 further evaluated the proportionality of 1 × 4- versus 4 × 1-mg doses. Safety was also monitored. Findings/results: There were 43, 27, and 29 subjects who completed studies 1, 2, and 3, respectively. The 90% confidence intervals for Cmax,SS , Cmin , and AUC TAU,SS of once-daily ER lorazepam compared with IR given TID were within 80% to 125% limits establishing steady-state bioequivalence. Maximum mean lorazepam concentrations were achieved at 11 hours compared with 1 hour after dosing for ER versus IR lorazepam, respectively. Pharmacokinetic parameters ( Cmax , AUC last or AUC 0- t , AUC inf or AUC 0-inf ) of ER lorazepam were bioequivalent whether taken with or without food, administered intact or sprinkled onto food, or administered as intact 1 × 4- versus 4 × 1-mg capsules. No serious safety concerns were found. Implications/conclusions: Once-daily ER lorazepam provided a pharmacokinetic profile bioequivalent to IR lorazepam given TID and was well tolerated in healthy adults across all phase 1 studies. These data suggest that ER lorazepam could be an alternative for patients currently treated with IR lorazepam. |
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Mesh-Begriff(e) | Adult ; Humans ; Lorazepam/adverse effects ; Delayed-Action Preparations ; Cross-Over Studies ; Area Under Curve |
Chemische Substanzen | Lorazepam (O26FZP769L) ; Delayed-Action Preparations |
Sprache | Englisch |
Erscheinungsdatum | 2023-06-19 |
Erscheinungsland | United States |
Dokumenttyp | Clinical Trial, Phase I ; Journal Article |
ZDB-ID | 604631-9 |
ISSN | 1533-712X ; 0271-0749 |
ISSN (online) | 1533-712X |
ISSN | 0271-0749 |
DOI | 10.1097/JCP.0000000000001715 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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