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2023 ◽  
Author(s):  
Matthieu Clertant ◽  
Nolan A. Wages ◽  
John O'Quigley

2022 ◽  
Author(s):  
Christina Yap ◽  
Alun Bedding ◽  
Johann de Bono ◽  
Munyaradzi Dimairo ◽  
Aude Espinasse ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2171
Author(s):  
Tamás Jordán ◽  
Orsolya Basa-Dénes ◽  
Réka Angi ◽  
János Orosz ◽  
Zsolt Ötvös ◽  
...  

Currently approved formulations of the androgen synthesis inhibitor abiraterone acetate (AA) consist of multiple tablets administered daily in a fasted state. Removing the food effect and switching to a suspension formulation is expected to improve the pharmacokinetic profile and facilitate drug administration for patients with late-stage prostate cancer. Two four-sequence, four-period randomized crossover investigations were undertaken to establish the pharmacokinetic profiles of single doses of commercially available Zytiga®, as the reference AA (R-AA), and a novel tablet for oral suspension (TOS). Four single doses of TOS (from 62.5 to 250 mg) were compared in study C01, and two single doses each of TOS (250 mg) and R-AA (1000 mg) were compared under fasted and fed (modified fasted for R-AA) conditions in C02. Plasma concentrations of abiraterone over time were measured, and pharmacokinetic parameters were calculated. Each doubling of the dose of TOS was associated with a greater than 3-fold increase in exposure. A single dose of TOS (250 mg) exhibited similar exposure over 24 h, whether given fasted (625 ng × h/mL) or fed (485 ng × h/mL). A single dose of TOS (250 mg) was associated with higher (fasted, p = 0.028) or equivalent exposure (fed) compared to 1000 mg R-AA fasted (532 ng × h/mL). Substantially higher exposures were seen with 1000 mg R-AA under modified fasted conditions compared to TOS, irrespective of prandial status (p < 0.001). TOS was generally safe and well tolerated in the study. A 250 mg dose of a novel AA formulation for oral suspension demonstrated bioequivalence to 1000 mg R-AA under fasted conditions. This novel TOS formulation also addresses some of the limitations of current AA treatment, including low bioavailability, high variability in systemic exposure and a large food effect. It may offer an alternative for patients with dysphagia or discomfort with swallowing large pills.


2021 ◽  
Author(s):  
Pavel Mozgunov ◽  
Suzie Cro ◽  
Anne Lingford‐Hughes ◽  
Louise M. Paterson ◽  
Thomas Jaki

Hepatology ◽  
2021 ◽  
Author(s):  
Cihan Yurdaydin ◽  
Onur Keskin ◽  
Esra Yurdcu ◽  
Aysun Çalişkan ◽  
Soner Önem ◽  
...  

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Andrea Baker ◽  
Lachlan Clarke ◽  
Peter Donovan ◽  
Jacobus P. J. Ungerer ◽  
Gunter Hartel ◽  
...  

Abstract Background Schizophrenia is a persistent psychotic disorder often accompanied by severe disability and premature mortality. New pharmacological treatments are urgently needed. Sodium benzoate, a common food preservative holds potential to be an effective, accessible treatment for schizophrenia, though the optimal dosing and mechanism of action of the compound requires further investigation. Methods Individuals with persistent treatment-refractory schizophrenia (n=52) will be recruited. Patients will be randomised in a 1:1:1:1 ratio to receive treatment of one of three active doses (1000, 2000 or 4000 mg daily) of sodium benzoate or placebo for 6 weeks duration. The primary outcome measurement is change in the Positive and Negative Syndrome Scale (PANSS) total score. Secondary outcome measurements are PANSS subscales, Global Assessment of Function (GAF), Clinical Global Impression (CGI) and Patient Global Impression (PGI-I). Change in concentrations of peripheral amino acids (D-alanine, L-alanine, D-serine, L-serine, glycine and glutamate), plasma sodium benzoate, plasma catalase, 3-nitrotyrosine, malondialdehyde and high-sensitivity C-reactive protein (hs-CRP) will be determined as tertiary measures. Discussion This trial seeks to build upon previous research indicating potential efficacy of sodium benzoate for reduction of symptoms in individuals with treatment-refractory schizophrenia. The trial aims to improve the understanding of the mechanism of action of the compound. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000327886. Registered on 23 March 2021.


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