Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study

Bækdal, Tine A.; Donsmark, Morten; Hartoft‐Nielsen, Marie‐Louise; Søndergaard, Flemming L.; Connor, Alyson

doi:10.1002/cpdd.938

Cited by 19 publications

(18 citation statements)

References 26 publications

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“…10 The ability of SNAC to improve drug absorption has been demonstrated in many studies. 11,12 N-AbA was developed to promote the gastrointestinal absorption, low oral bioavailability, high pharmacokinetic variability, and food effects of abiraterone. Here, we conducted this study aimed at comparing the pharmacokinetic characteristics, safety, and food effects of N-AbA and R-AbA.…”

Section: Introductionmentioning

confidence: 99%

Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

Feng¹,

Liu²,

Kuang³

et al. 2022

DDDT

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Abiraterone acetate tablets (I)(N-AbA) is a novel tablet co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). This study aimed to compare the pharmacokinetics, bioequivalence, safety, and food effects of N-AbA with the reference ZYTIGA ® (R-AbA) in healthy Chinese male subjects. Patients and Methods: This study was conducted in three parts. Part I was an open, doseescalation trial conducted in 16 Chinese healthy males; Part II was a randomized, open-label, 2 × 4 crossover, single-dose bioequivalence trial conducted in 36 subjects; Part III was a randomized, 3 × 3 crossover trial conducted on 24 volunteers to investigate the effect of food on the pharmacokinetics of N-AbA. Results:The exposure (AUC 0-∞ ) and maximum concentration (C max ) of abiraterone and excipient SNAC were linear in the range of 75-450 mg dose. The bioavailability of N-AbA 300 mg was equivalent to that of R-AbA 1000 mg. The drug exposure of prednisone and prednisolone was not affected by SNAC co-administration. The C max of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC 0-∞ was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The C max and AUC 0-∞ of orally administered abiraterone as N-AbA on a high-fat diet were 2.2 times and 2 times, respectively, higher than those on a fasting state. All adverse events reported in the three parts of the study were grade 1 or 2, and no serious adverse events were reported. Conclusion: These three Phase I trials showed that N-AbA and excipient SNAC had excellent linear pharmacokinetic characteristics. A single dose of N-AbA 300 mg was bioequivalent to R-AbA 1000 mg in healthy subjects under fasting conditions. Meanwhile, SNAC had no effect on the pharmacokinetics of prednisone and prednisolone. The effect of food on N-AbA was significantly lower than that on R-AbA.

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Section: Introductionmentioning

confidence: 99%

Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

Feng¹,

Liu²,

Kuang³

et al. 2022

DDDT

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“…Several reasons may be present, which are i) he could take the medicine regularly every morning, ii) he has continued the lifestyle with rare breakfast, iii) he can keep fasting 90-120 min post-med. When the fasting period becomes more, the blood concentration is increased from several experimental data of Rybelsus [22]. When comparing the blood concentration of semaglutide, 0.80 for 30 min fasting and 1.39 for 120 min fasting [23].…”

Section: Discussionmentioning

confidence: 99%

Rapid Reduction of HbA1c and Weight in Elderly Patient with Type 2 Diabetes (T2D) And Depression by Oral Semaglutide (Rybelsus)

Bando

Hayashi

SUMITOMO

et al. 2022

Asp Biomed Clin Case Rep

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Background: Oral semaglutide (Rybelsus) has been in focus for type 2 diabetes (T2D). Case Presentation: The patient is a 73-year-old male with T2D treated with metformin, Ipragliflozin, and rosuvastatin. He was diagnosed with depression by the Geriatric depression scale (GDS) with a stable condition by mirtazapine. His diabetic control was exacerbated to HbA1c 8.8% and weight 63.5kg in Feb 2022. Results: He started to take Rybelsus, and then clinical improvement was found as HbA1c 6.9% and weight 57.5kg for 4 months. Discussion: Remarkable effect of HbA1c and weight may be from longer fasting time after post-med, and regular lifestyle from the stable psychosomatic situation.

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“…On the basis of the results from the dosing conditions trial, semaglutide plasma exposure is similar when oral semaglutide is administered with 120 versus 50 mL water. Still, another study found that semaglutide exposure was reduced by approximately 40% when administered with 240 versus 50 mL water [ 22 ], suggesting that greater than 120 mL water with dosing may negatively influence the absorption of oral semaglutide. Interestingly, t 1/2,semaglutide,day10 was approximately 1 week in all treatment arms of the two current trials, showing that in contrast to absorption, the metabolism and elimination of semaglutide are not affected by food ingestion or water volume with dosing as expected.…”

Section: Discussionmentioning

confidence: 99%

Effect of Various Dosing Conditions on the Pharmacokinetics of Oral Semaglutide, a Human Glucagon-Like Peptide-1 Analogue in a Tablet Formulation

Bækdal

Breitschaft²,

Donsmark

et al. 2021

Diabetes Ther

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Introduction: Oral semaglutide is a novel tablet formulation of the human glucagon-like peptide-1 analogue semaglutide. In two trials, the effects of prior food ingestion (food effect), post-dose fasting period and water volume with dosing (dosing conditions) on oral semaglutide pharmacokinetics were investigated. Methods: Subjects received once-daily oral semaglutide for 10 days. In the food-effect trial, 78 healthy subjects were randomised 1:1:1 to fed (meal 30 min pre-dose; 240 mL water with dosing), fasting (overnight until 4 h post-dose; 240 mL) or reference (fasting overnight until 30 min post-dose; 120 mL) arms. In the dosing conditions trial, 161 healthy men were randomised into eight dosing groups (overnight fasted with 50/120 mL water and 15/30/60/ 120 min post-dose fasting). Semaglutide plasma concentrations were measured frequently until 504 h after the 10th dose. Results: In the food-effect trial, limited or no measurable semaglutide exposure was observed in the fed arm, while all subjects in the fasting arm had measurable semaglutide exposure. Area under the semaglutide concentration-time curve (AUC 0-24h,semaglutide,day10 ) and maximum semaglutide concentration (C max,semaglutide,day10 ) were numerically greater by approximately 40% for the fasting versus reference arm (p = 0.082 and p = 0.080, respectively). In the dosing conditions trial, AUC 0-24h,semaglutide,day10 and C max,semaglutide,day10 were not different between water volumes (p = 0.541 and p = 0.676), but increased with longer post-dose fasting (p \ 0.001). Conclusion:Administration of oral semaglutide in the fasting state with up to 120 mL water and at least 30 min post-dose fasting results in clinically relevant semaglutide exposure. These dosing conditions have been used in the oral semaglutide phase 3 trials and are part of the approved label.Trial Registration: ClinicalTrials.gov identifiers NCT02172313, NCT01572753.

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Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study

Cited by 19 publications

References 26 publications

Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

Rapid Reduction of HbA1c and Weight in Elderly Patient with Type 2 Diabetes (T2D) And Depression by Oral Semaglutide (Rybelsus)

Effect of Various Dosing Conditions on the Pharmacokinetics of Oral Semaglutide, a Human Glucagon-Like Peptide-1 Analogue in a Tablet Formulation

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