Dataset Information

Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.

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.

SUBMITTER: Mathew SJ

PROVIDER: S-EPMC10309101 | biostudies-literature | 2023 Jul-Aug 01

REPOSITORIES: biostudies-literature

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Publications

Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.

Mathew Sanjay J SJ Jean-Lys Shedly S Phull Rupinder R Yarasani Rama R

Journal of clinical psychopharmacology 20230619 4

<h4>Purpose/background</h4>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.<h4>Methods/procedures</h4>These phase 1 studies assessed the pharmacokinetics of ER lorazepam administered: (study 1) 3 mg once daily ...[more]

PMID: 37335199

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Dataset Information

Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.

Purpose/background

Methods/procedures

Findings/results

Implications/conclusions

Publications

Characterization of Extended-Release Lorazepam: Pharmacokinetic Results Across Phase 1 Clinical Studies.

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