Abstracts
3427188
(#23) A Randomized Crossover Study Evaluating the Bioavailability of a Once-Daily Dose Lithium Carbonate Extended-Release Bi-Layer Matrix Formulation Across Regimens in Healthy Adults Under Fed Conditions
Abstract: Purpose: Bioavailability of a novel once-daily (QD) lithium carbonate extended-release (XR) 900 mg formulation was compared with two approved reference regimens: two-times-daily (BID) lithium carbonate ER 450 mg and three-times-daily (TID) lithium carbonate immediate-release (IR) 300 mg. The primary objective was to compare the rate and extent of absorption following a single dose under fed conditions.
Methods: This open-label, balanced, randomized, three-period, three-treatment, six-sequence, three-way crossover study was conducted in healthy adult volunteers. Participants received a total dose of 900 mg of each formulation under fed conditions per assigned treatment sequence. The total study duration was 37 days with ≥14-day washout periods between dosing periods. Plasma lithium concentrations were quantified via validated ICP-OES. Primary pharmacokinetic (PK) parameters included Cmax, AUC0-t, and AUC0-∞. Bioequivalence was assessed using ln-transformed PK parameters and 90% CIs for geometric least-squares mean ratios.
Results: Twenty-five participants completed ≥2 study periods. Mean (±SD) Cmax values were 4067.90 ± 817.30, 4049.80 ± 670.00, and 3708.30 ± 540.60 ng/mL for QD XR, BID ER, and TID IR, respectively. Corresponding AUC0-t values were 125,690.90 ± 31,739.00, 128,152.50 ± 21,257.30, and 117,254.10 ± 17,645.90 hr*ng/mL. Median Tmax was 12 h for QD XR versus 18.00 h for BID ER and 20.00 h for TID IR. All 90% CIs were within bioequivalence criteria of 80.00%-125.00%. Treatments were well tolerated.
Conclusions: The novel QD lithium carbonate XR 900 mg formulation was bioequivalent to BID ER and TID IR lithium carbonate under fed conditions, supporting a simplified once-daily dosing regimen.
Short Description: This open-label, randomized, three-way crossover bioequivalence study compared a novel once-daily (QD) lithium carbonate extended-release (XR) 900 mg formulation with twice-daily (BID) extended-release (ER) 450 mg and three-times-daily (TID) immediate-release (IR) 300 mg formulations in healthy adults under fed conditions. Pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) met bioequivalence criteria (90% CIs within 80.00%-125.00%), demonstrating that the simplified QD XR regimen provides comparable absorption to approved multiple-daily-dose formulations.
Name of Sponsoring Organization(s):
Methods: This open-label, balanced, randomized, three-period, three-treatment, six-sequence, three-way crossover study was conducted in healthy adult volunteers. Participants received a total dose of 900 mg of each formulation under fed conditions per assigned treatment sequence. The total study duration was 37 days with ≥14-day washout periods between dosing periods. Plasma lithium concentrations were quantified via validated ICP-OES. Primary pharmacokinetic (PK) parameters included Cmax, AUC0-t, and AUC0-∞. Bioequivalence was assessed using ln-transformed PK parameters and 90% CIs for geometric least-squares mean ratios.
Results: Twenty-five participants completed ≥2 study periods. Mean (±SD) Cmax values were 4067.90 ± 817.30, 4049.80 ± 670.00, and 3708.30 ± 540.60 ng/mL for QD XR, BID ER, and TID IR, respectively. Corresponding AUC0-t values were 125,690.90 ± 31,739.00, 128,152.50 ± 21,257.30, and 117,254.10 ± 17,645.90 hr*ng/mL. Median Tmax was 12 h for QD XR versus 18.00 h for BID ER and 20.00 h for TID IR. All 90% CIs were within bioequivalence criteria of 80.00%-125.00%. Treatments were well tolerated.
Conclusions: The novel QD lithium carbonate XR 900 mg formulation was bioequivalent to BID ER and TID IR lithium carbonate under fed conditions, supporting a simplified once-daily dosing regimen.
Short Description: This open-label, randomized, three-way crossover bioequivalence study compared a novel once-daily (QD) lithium carbonate extended-release (XR) 900 mg formulation with twice-daily (BID) extended-release (ER) 450 mg and three-times-daily (TID) immediate-release (IR) 300 mg formulations in healthy adults under fed conditions. Pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞) met bioequivalence criteria (90% CIs within 80.00%-125.00%), demonstrating that the simplified QD XR regimen provides comparable absorption to approved multiple-daily-dose formulations.
Name of Sponsoring Organization(s):
