Randomized, Open-Label, Single-Dose, Crossover, Relative Bioavailability Study in Healthy Adults, Comparing the Pharmacokinetics of Rabeprazole Granules Administered Using Soft Food or Infant Formula as Dosing Vehicle Versus Suspension

Gepotidacin is a novel, first-in-class triazaacenaphthylene antibiotic that may provide a new treatment option for antibiotic-resistant pathogens. Two pharmacokinetic evaluations of oral gepotidacin are presented; a relative bioavailability study that guided formulation development, followed by an adult and adolescent study of the final formulation. In the relative bioavailability study, after gepotidacin administration to 26 healthy adults as free base roller compacted (RC) tablets, free base high shear wet granulation (HSWG) tablets, and mesylate salt reference capsules, the RC tablet exposure ratios and 90% confidence intervals (CIs) were within the 0.80 to 1.25 confidence bounds; however, the HSWG tablet maximum observed concentration (C max ) was higher compared to the reference (ratio: 1.15; 90% CIs: 1.0113, 1.3047). In the healthy adult (n=16) and adolescent (n=17) study, a gepotidacin mesylate salt tablet was evaluated as a 1,500-mg single dose, 2 doses administered 6 or 12 h apart (6,000 mg total), or placebo. Single-dose mean C max was ∼27% higher in adolescents versus adults and area under the concentration-time curve (AUC) was comparable in both populations. After 2 doses were administered, mean C max was similar for both ages and mean AUC was ∼35% higher in adolescents versus adults. Concentrations increased proportionally with dose. Safety-risk profiles were similar in both ages. Across studies, the most common adverse events were gastrointestinal. Overall, the pharmacokinetics of the final gepotidacin mesylate salt tablet have been well-characterized, enrollment of adolescents into the pivotal trials is supported, and dosing intervals were determined that should provide adequate exposures for microbiological efficacy.

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Comparative single-dose bioavailability study of two 10 mg Zolpidem tablet formulations in healthy volunteers

Macedonian Pharmaceutical Bulletin ◽

10.33320/maced.pharm.bull.2019.65.01.002 ◽

2019 ◽

Vol 65 (01) ◽

pp. 11-17

Author(s):

Dimce Zafirov ◽

Jasmina Trojacanec ◽

Dragica Zendelovska ◽

Nikola Kolovcevski ◽

Bojan Labachevski

Keyword(s):

Single Dose ◽

Healthy Volunteers ◽

Plasma Concentrations ◽

Bioequivalence Study ◽

Relative Bioavailability ◽

Serious Adverse Events ◽

Test Formulation ◽

Single Oral Administration ◽

Hypnotic Agent ◽

Bioavailability Study

Zolpidem is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs with known hypnotic properties. Zolpidem as conventional tablets is used as a hypnotic agent in the short-term management of insomnia, generally for periods not exceeding 7–10 days in duration. The objective of this study was to evaluate and compare the relative bioavailability, and therefore the bioequivalence of Zolpidem 10 mg test formulation versus a reference Zolpidem 10 mg formulation, following a single dose administration under fasting conditions The study was a single center, open, single dose, randomized, two - way crossover study in healthy male volunteers with a wash - out period of one week between study periods. Twenty-eight male healthy volunteers, aged 20-49 years were included into study. Blood samples for determination of zolpidem plasma concentrations were withdraw at 0 (pre-drug administration), 0.33, 0.66, 1, 1.33, 1.66, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 16 and 24 hours post-drug. The zolpidem concentrations in plasma were determined with HPLC, using fluorescence detection. The test formulation of zolpidem, dosed at 10 mg is bioequivalent for primary zolpidem parameters (Cmax, AUC0-t and AUC0-∞) to the reference formulation after a single oral administration of 10 mg zolpidem. Both medications are well tolerated with no serious adverse events. Thus, in view of the clinical use, both formulations are exchangeable without restrictions. Keywords: Zolpidem, bioavailability, bioequivalence study, single-dose

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A Single Dose, Four-Way, Open-Label Bioavailability Study of Oral Acetaminophen and Ibuprofen Combinations (Maxigesic®) under both Fasting and Fed Conditions

Journal of Bioequivalence & Bioavailability ◽

10.4172/0975-0851.1000383 ◽

2018 ◽

Vol 10 (5) ◽

Author(s):

Phillip Aitken ◽

Isam I Salem ◽

Ioana Stanescu ◽

Rebecca Playne ◽

Hartley C Atkinson

Keyword(s):

Single Dose ◽

Open Label ◽

Bioavailability Study

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0745 The Pharmacokinetics of FT218, Once Nightly Sodium Oxybate: Food Effect and Bioavailability Compared to Twice Nightly Sodium Oxybate

SLEEP ◽

10.1093/sleep/zsaa056.741 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A283-A283

Author(s):

M Thorpy ◽

D Seiden ◽

J Grassot ◽

D Monteith ◽

J Dubow ◽

...

Keyword(s):

Single Dose ◽

Controlled Release ◽

Food Effect ◽

Relative Bioavailability ◽

Sodium Oxybate ◽

Pharmacokinetic Studies ◽

Release Formulation ◽

Fed State ◽

Fasted State ◽

Bioavailability Study

Abstract Introduction Sodium oxybate is an effective treatment for excessive daytime sleepiness and cataplexy in patients with narcolepsy. The FDA approved formulation requires twice-nightly dosing; at bedtime and 2.5 - 4 hours later. FT218 is a controlled-release formulation of sodium oxybate intended for once-nightly dosing, using Avadel’s proprietary Micropump™ technology. The objective of this study was to evaluate the relative bioavailability of investigational once-nightly sodium oxybate, FT218, 6 g, compared to commercially available twice-nightly sodium oxybate and the food effect of FT218. Methods Two crossover, single-dose pharmacokinetic studies were conducted in healthy volunteers. The first, a relative bioavailability study (n=28) was completed comparing FT218 6 g to twice-nightly sodium oxybate 6 g (in two divided doses of 3 g). The second, evaluated the food effect (n=16) of FT218 6g in the Fed vs. Fasted state. Results FT218 had a lower overall Cmax than twice-nightly sodium oxybate, while AUC was equivalent. C8h level and variability was comparable between FT218 and twice-nightly sodium oxybate. In the Fed, compared to the Fasted state, FT218 had a longer Tmax, lower Cmax and decreased AUC (Cmax 67%, AUC 86%, Tmax 1-hour slower than Fasted values). Adverse Events with FT218 were mostly mild or moderate in severity, non-serious and known AEs associated with sodium oxybate. The safety profiles of FT218 and twice-nightly sodium oxybate at 6 g appeared similar. Conclusion Once-nightly FT218 at 6 g demonstrated a lower overall Cmax and similar exposure to twice-nightly sodium oxybate, with similar C8h plasma levels and C8h variability. In the Fed state, AUC and Cmax of FT218 was lower than in the Fasted State. FT218 was generally safe and well tolerated and the safety profile appeared comparable to twice-nightly sodium oxybate. Support This work was supported by Avadel Pharmaceuticals.

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