A randomized, open-label, 2-period, crossover bioequivalence study of two oral formulations of 75 mg oseltamivir in healthy Thai volunteers

2008 ◽  
Vol 46 (12) ◽  
pp. 654-662 ◽  
Author(s):  
S. Kongpatanakul ◽  
S. Chatsiricharoenkul ◽  
U. Panich ◽  
K. Sathirakul ◽  
P. Pongnarin ◽  
...  
Keyword(s):  
Bioequivalence Study ◽  
Open Label ◽  
Oral Formulations

Has the Time Come to Employ Population and Individual Bioequivalence for the Evaluation of Generics?

2020 ◽  
Vol 21 (2) ◽  
pp. 112-125
Author(s):  
Francis Micheal ◽  
Mohanlal Sayana ◽  
Rajendra Prasad ◽  
Balamurali Musuvathi Motilal
Keyword(s):  
Therapeutic Index ◽  
Bioequivalence Study ◽  
Open Label ◽  
Statistical Parameters ◽  
Population Mean ◽  
Average Bioequivalence ◽  
Individual Bioequivalence ◽  
Population Bioequivalence ◽  
Enteric Coated ◽  
Bioequivalence Assessment

Background: Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses drug interchangeability as it considers only population mean for the evaluation especially when highly variable drug products and narrow therapeutic index drugs are dealt with. Hence, the alternative approaches like population bioequivalence and individual bioequivalence assessment approaches emerge as they consider inter/intra-subject variance and subject- by-formulation variance along with population mean. Objectives: The objective of the study was to apply different bioequivalence assessment approaches in a replicate bioequivalence study to evaluate the drug interchangeability. Methods: This was an open-label, single-dose, randomized, balanced, two-treatment, three-period, three-sequence, partial replicate crossover bioequivalence study of omeprazole enteric-coated tablet 20 mg conducted on 48 normal healthy subjects under fed conditions. The plasma concentration of omeprazole was analyzed by a validated bioanalytical method to determine the pharmacokinetic and statistical parameters to assess average bioequivalence, population bioequivalence, and individual bioequivalence. Results: In this study, test formulation was shown to be bio-inequivalent to the reference formulation by average bioequivalence, population bioequivalence, and individual bioequivalence approaches. Conclusion: The outcome of the evaluation clearly states that the bioequivalence outcome of all these approaches are the same. Obviously, it does not mean that these three approaches provide the same outcome though the consideration of variances varies. Certainly, population bioequivalence and individual bioequivalence approach will be more accurate for the assessment of drug interchangeability.

Bioavailability of Two Single-Dose Oral Formulations of Omeprazole 20 mg: An Open-Label, Randomized Sequence, Two-Period Crossover Comparison in Healthy Mexican Adult Volunteers

2008 ◽  
Vol 30 (4) ◽  
pp. 693-699 ◽  
Author(s):  
Jorge Luis Poo ◽  
Juan Francisco Galán ◽  
Alejandra Rosete ◽  
Alberto de Lago ◽  
Iván Oliva ◽  
...  
Keyword(s):  
Single Dose ◽  
Open Label ◽  
Oral Formulations ◽  
Dose Oral ◽  
Adult Volunteers ◽  
Crossover Comparison

Pharmacokinetics and bioequivalence of generic etoricoxib in healthy volunteers

2021 ◽  
Vol 10 (3) ◽  
pp. 113-118
Author(s):  
Nishalini Harikrishnan ◽  
Ka-Liong Tan ◽  
Kar Ming Yee ◽  
Alia Shaari Ahmad Shukri ◽  
Nalla Ramana Reddy ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Bioequivalence Study ◽  
Active Pharmaceutical Ingredient ◽  
Pharmacokinetic Profile ◽  
Time Profile ◽  
Pharmacokinetic Parameters ◽  
Open Label ◽  
Reference Drug ◽  
Test Formulation ◽  
R Ratio

Introduction/Study Objectives: A bioequivalence study was performed to compare the pharmacological profile of innovator etoricoxib (ETO) with a newly developed generic ETO, both in a 120 mg tablet formulation. A dissolution study was conducted to optimize the formulation process before evaluating physical changes in the active pharmaceutical ingredient and the formulated product. Methods: This was a randomized, open-label, balanced, two-treatment, two-period, two-sequence, single-dose, two-way crossover, truncated bioequivalence study involving a washout period of ten days. A total of 26 healthy male volunteers were recruited. The pharmacokinetic profile of the test formulation was compared with the reference formulation. Results/Discussion: The pharmacokinetic parameters of ETO were calculated based on the plasma drug concentration-time profile using non-compartmental analysis to determine its safety profile and tolerability. The Test/Reference (T/R) ratio of ETO was 104.36% (90% confidence interval (CI): 98.30%–110.80%) for area under curve (AUC)0-72 while the T/R ratio of maximum concentration (Cmax) was 101.39% (92.15%–111.56%). The 90% CI of the Cmax and AUC0-72 of ETO were within acceptable bioequivalence limits of 80%–125%. All values were within the predetermined limits of the Association of Southeast Asian Nation (ASEAN) bioequivalence guidelines. Conclusion: The test formulation was found to be bioequivalent with respect to the reference drug, according to ASEAN bioequivalence guidelines.

scholarly journals Levocetirizine Oral Disintegrating Tablet: A Randomized Open‐Label Crossover Bioequivalence Study in Healthy Japanese Volunteers

2020 ◽  
Vol 9 (7) ◽  
pp. 805-812
Author(s):  
Hiroko Ino ◽  
Masanari Shiramoto ◽  
Takashi Eto ◽  
Miwa Haranaka ◽  
Shin Irie ◽  
...  
Keyword(s):  
Bioequivalence Study ◽  
Open Label ◽  
Oral Disintegrating Tablet

scholarly journals Safety, Tolerability, and Pharmacokinetics (PK) of Posaconazole (POS) Intravenous (IV) Solution and Oral Powder for Suspension in Children With Neutropenia

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S296-S296 ◽  
Author(s):  
Andreas H Groll ◽  
Hisham Abdel-Azim ◽  
Thomas Lehrnbecher ◽  
William Steinbach ◽  
RoseAnn Murray ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Age Groups ◽  
Oral Suspension ◽  
Target Range ◽  
Age Group ◽  
Open Label ◽  
Dose Escalation Study ◽  
Oral Formulations ◽  
Younger Age ◽  
Dose Levels

Abstract Background POS, a triazole antifungal approved for prophylaxis and treatment of adults with invasive fungal infections, is available as an IV solution and 2 oral formulations: an oral suspension and a tablet with improved bioavailability. A novel powder for oral suspension (PFS) has been developed to offer the bioavailability of the tablet in a formulation optimized for weight-based dosing in children. The objective of this study is to evaluate the safety, tolerability, and PK of POS IV and POS PFS in pediatric patients (patients) aged 2 to 17 y with documented or expected neutropenia. Methods This is an ongoing, nonrandomized, multicenter, open-label, sequential dose-escalation study evaluating POS IV and POS PFS. Pts are divided into 2 age groups: 2 to <7 and 7 to 17 y. Each age group includes 2 dose cohorts: 3.5 mg/kg/d and 4.5 mg/kg/d. Patients received 10–28 d of POS initially as IV solution with the option to switch to PFS after 10 d for the remainder of the treatment period. PK sampling was conducted after 7–10 days on each formulation. Target PK exposure was ~90% of patients with Cavg 500–2,500 ng/mL. Cavg is defined as AUC over a dosing interval. Results 57 of 66 patients (86%) who received POS IV were PK evaluable; 35 patients (53%) received POS PFS, of whom 30 (86%) were PK evaluable. Table 1 shows Cavg and proportion in target range of PK-evaluable patients by dose cohort and age group. The safety profiles of POS IV and PFS were similar to those previously reported for adults treated with oral/IV POS. Conclusion POS PFS resulted in lower POS exposure than IV across age groups at both dose levels. POS exposure was substantially lower in the younger age group for both IV and PFS. At 4.5 mg/kg, the patients in this study achieved the predefined target but did not achieve systemic exposures (mean Cavg) comparable to those seen in adults with POS IV or tablet. These results suggest that study of POS IV and PFS dosing >4.5 mg/kg/d is warranted. Disclosures A. H. Groll, Merck Sharp & Dohme: Consultant, Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. T. Lehrnbecher, Merck/MSD: Scientific Advisor and Speaker’s Bureau, Speaker honorarium. Astellas: Scientific Advisor and Speaker’s Bureau, Speaker honorarium. Basilea: Scientific Advisor, Consulting fee. Gilead: Investigator, Scientific Advisor and Speaker’s Bureau, Research grant and Speaker honorarium.Pfizer: Speaker’s Bureau, Speaker honorarium. W. Steinbach, Merck: Consultant, Consulting fee. Astellas: Consultant, Consulting fee. Gilead: Consultant, Consulting fee. R. Murray, Merck: Employee, Salary. A. Paschke, Merck: Employee, Salary. E. Mangin, Merck: Employee, Salary. G. A. Winchell, Merck: Research Contractor, Consulting fee. C. J. Bruno, Merck: Employee and Shareholder, Salary and Stock.

scholarly journals A Randomized, Open-label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects

2016 ◽  
pp. AAC.01393-16 ◽  
Author(s):  
Haiying Sun ◽  
Lillian Ting ◽  
Surendra Machineni ◽  
Jens Praestgaard ◽  
Andreas Kuemmell ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Geometric Mean ◽  
Oral Solution ◽  
Tablet Formulation ◽  
Absolute Bioavailability ◽  
Open Label ◽  
Phase 3 ◽  
Total Exposure ◽  
Oral Formulations ◽  
Tablet Formulations

Omadacycline is a first in class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes, and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The bioavailability of a Phase 3 tablet formulation relative to intravenous (IV) administration (and of other oral formulations relative to the Phase 3 tablet) was investigated in an open-label, randomized, four-period, crossover study in healthy subjects age 18-50 years. Subjects received omadacycline 100 mg IV, 300 mg oral as two different tablet formulations with different dissolution profiles, and a 300 mg as an oral solution. Plasma omadacycline concentrations were determined using a validated LC/MS/MS method. Twenty of 24 subjects completed all treatment periods. Both tablet formulations produced equivalent total exposure relative to each other. The Phase 3 tablet produced equivalent exposure to the 100 mg IV dose with geometric mean ratio (90% confidence intervals [CI]) for AUCinfof 1.00 (0.93,1.07). Absolute bioavailability of the tablets was approximately 34.5%. Intersubject variability was consistent among the oral formulations (∼20-25%). Single oral and IV doses of omadacycline were well tolerated; three subjects experienced mild adverse events (dizziness, nausea, vomiting) that resolved without intervention. A 300 mg dose of the tablet formulation of omadacycline intended for use in phase 3 studies produced total exposure equivalent to that of a 100 mg IV dose.

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