9^th World Congress on Bioavailability & Bioequivalence April 16-18, 2018 Dubai,UAE

Chutima Manamuti currently working as a researcher of Bioequivalence Study Group, Research and Development Institute, the Government Pharmaceutical Organization (GPO), Bangkok, Thailand responsible for method development, method validation and bioanalysis in biological fluids. The Government Pharmaceutical Organization (GPO) is a state enterprise under the Ministry of Public Health of Thailand which dedicated itself to the Thai society in providing better standing of living for all Thais through a production and supply of quality medicines at affordable prices.

Quetiapine is an atypical antipsychotic which is indicated for the treatment of schizophrenia, bipolar depression and mania. A generic product of quetiapine has been developed with lower price by the Government Pharmaceutical Organization (GPO) to be an alternative choice of related physicians and patients who will gain access to the lower price medicines at the same quality and safety as the reference product. A comparative randomized, single dose, two-way crossover, open-label bioequivalence study of a generic quetiapine 25 mg tablets formulations, Quapine of GPO, Thailand and the reference product, Seroquel of AstraZeneca Pharmaceutical Co., Ltd. in healthy Thai volunteers under fasting conditions was conducted with 7 days wash-out period between the treatments to compare the rate and extent of absorption and evaluate the safety of the formulations. Blood samples were collected at predefined time points up to 48 hours and centrifuged to separate the plasma. Plasma samples were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Non-compartmental model was used for pharmacokinetic analysis and statistical analysis. The 90% parametric confidence intervals for the ln-transformed test/reference ratios of primary pharmacokinetic parameter, AUC0-tlast, AUC0-∞ and Cmax were 102.0 (96.08-108.33), 102.1 (96.21-108.31) and 108.1 (96.52-121.09), respectively for quetiapine. These values were within the acceptable range of 80.00-125.00. These results showed that both formulations were bioequivalent in terms of rate and extent of absorption. Therefore, this study confirmed that both formulations can be used interchangeably.

Min Wu, Master in pharmaceutical chemistry (2013), Jilin University School of Pharmaceutical Sciences, China Working experience: As an Quality Assurance (2014-present) in Department of Phase I Clinical Trials Unit Responsible for: 1. More than 10 Phase I Clinical Trials 2. More than 20 BE and PK studies of chemical drugs

Prostate cancer is the second-and third-leading cause of cancer-related deaths in men and tumor growth is usually dependent on circulating androgens. Abiraterone acetate is a prodrug of abiraterone, a selective irreversible inhibitor of cytochrome P 17a-hydroxylase/C17, 20-lyase that plays a key role in the production of androgens. Abiraterone is categorized into biopharmaceutics classification system(BCS) Class 4 (low solubility, low permeability) based on the importance of solubility and permeability on drug absorption, which adds the difficulty of obtaining the bioequivalence(BE) results. The aim of this study was to evaluate the BE of two abiraterone formulations (250-mg tablets) by the reference-scaled average bioequivalence (RSABE) approach, and to investigate the pharmacokinetic (PK) properties of Abiraterone in healthy Chinese subjects. This single-dose, open, randomized, four-way replicate study was conducted in healthy Chinese male volunteers under fasted (n=40) and fed (n=40) conditions. Blood samples were collected over a 72h period. Abiraterone concentrations were assayed using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. Abiraterone plasma Cmax, AUC0–t and AUC0-∞ were used to assess bioequivalence. Results showed that the 90% CIs for ratios of lnCmax, lnAUC0–t and lnAUC0-∞ for fasted study were 90.14-114.11, 93.96-115.07 and 93.72-113.331, respectively. For fed study, these data were 81.83-102.51, 91.51- 104.89 and 91.46-104.58, respectively. All of the 90% CIs were within the RSABE acceptance limits of the Chinese Food and Drug Administration(CFDA). Food intake increased the systemic exposure and Cmax to Abiraterone by 3-fold and 7-fold, respectively. The Swr of Cmax and AUC0-t for fasted study were 0.445 and 0.389. For fed study, these data were 0.444 and 0.281. The test and reference formulations of abiraterone met the regulatory criteria for bioequivalence of the CFDA. Abiraterone was safe and well tolerated at 250mg dose tested under fasted and fed condition.

Isariya Techatanawat currently working as a director of Bioequivalence Study Group, Research and Development Institute, the Government Pharmaceutical Organization (GPO), Bangkok, Thailand responsible for method development, method validation and bioanalysis in biological fluids. The Government Pharmaceutical Organization (GPO) is a state enterprise under the Ministry of Public Health of Thailand which dedicated itself to the Thai society in providing better standing of living for all Thais through a production and supply of quality medicines at affordable prices

Bioequivalence study of two deferasirox formulation, deferasirox GPO 250 mg dispersible tablets (test product) and Exjade 250 mg dispersible tablets (reference product) was carried out in this study. Thirty healthy Thai volunteers were randomized in a single dose, two-way crossover, open-label pharmacokinetics study with seven days washout period. All subjects completed treatments. After administration, blood samples were collected at predefined time points. Non-compartmental method was used to determine different pharmacokinetic parameters. The mean values ± SD of pharmacokinetic parameters for test and reference product, respectively, were follows, Cmax, 7819.767 ± 2231.5474 ng/mL and 8726.184 ± 2437.8461 ng/mL; AUC0-tlast, 98982.000 ± 30113.8029 ng.hr/mL and 104845.657 ± 39636.4390 ng.hr/mL; AUC0-∞, 104363.589 ± 31598.1583 ng.hr/mL and 110298.804 ±43203.8960 ng.hr/mL. No differences were detected between the formulations since the 90% Confidence Intervals of Cmax (89.7%, 84.09-95.60%), AUC0-tlast (96.4%, 91.19-101.92%) and AUC0-∞ (97.0%, 91.36-102.96%) were within the bioequivalent range. In conclusion, the test product (deferasirox GPO 250 mg dispersible tablets, manufactured by GPO, Thailand) when compared with the reference product (Exjade 250 mg dispersible tablets, manufactured by Novartis Pharma Stein AG, Switzerland) met the bioequivalence criteria (90% confident interval for the ratio of geometric least squares means within 80.00-125.00%) with respect to the rate and extent of absorption of deferasirox. Therefore, two formulations were bioequivalent and can be used interchangeably.

Doctor Souaad GUENDOUZ is a young researcher in the pharmaceutical field with a specialty diploma in pharmacology after a training in animal experimentation and the bioequivalence study at the national laboratory for the control of pharmaceuticals.

Determination of the solubility and permeability of the molecules allowed them to be classified into four categories according to the "BCS" classification system. This classification system can be used as a drug development tool to exonerate certain drugs from bioequivalence studies. The objective of the work is the classification of a molecule not classified BCS (Esomeprazole) by comparing its permeability with two molecules classified BCS one of which is highly permeable and the other is weakly permeable administered simultaneously in rats, using the model of intestinal perfusion in situ in anesthetized rats. Determination of the effective permeability is done in 4 anesthetized rats, by measuring the decay of the equilibrium luminal concentrations of the test molecule which is administered as a solution in infusion inside a segment of intestine maintained irrigated and innervated. It is sufficient to choose two molecules from the list of model molecules: one highly permeable (Naproxen - Metoprolol), and the other weakly permeable (Atenolol - Hydrochlorthiazide - Furosemide), for use as internal standards (include them in the infusion fluid, together with the test substance), in addition to the liquid flow marker (phenol red or other). The effective permeability of each molecule is calculated at steady state. Rats 1, 2 and 4 for which Esomeprazole / Atenolol / Metoprolol was administered simultaneously have results close to each other. Rat 3 has a very high effective permeability. Based on the published data, Metoprolol is classified as class I in BCS: high solubility, high permeability, Atenolol is class III in BCS: high solubility, low permeability; It can be concluded that our Esomeprazole study molecule has low permeability. Esomeprazole has a high solubility which allowed us to classify it in class III BCS.