Pharmacokinetic Comparison and Bioequivalence Evaluation of Two 20-mg Vonoprazan Fumarate Tablets in Bangladeshi Healthy Male Subjects  

作　　者：Md. Alimur Reza Uttom Kumar Bhowmik Sabrina Akter Tushi Nayan Ghosh Nithon Chandra Sahana Md. Ashraful Islam Nafisa Ahamed Arifa Akram Md. Alimur Reza;Uttom Kumar Bhowmik;Sabrina Akter Tushi;Nayan Ghosh;Nithon Chandra Sahana;Md. Ashraful Islam;Nafisa Ahamed;Arifa Akram(Novus Clinical Research Services Ltd., Dhaka, Bangladesh;Medical College for Women & Hospital, Dhaka, Bangladesh;National Institute of Laboratory Medicine & Referral Centre (NILMRC), Dhaka, Bangladesh)

机构地区：[1]Novus Clinical Research Services Ltd., Dhaka, Bangladesh [2]Medical College for Women & Hospital, Dhaka, Bangladesh [3]National Institute of Laboratory Medicine & Referral Centre (NILMRC), Dhaka, Bangladesh

出　　处：《Journal of Biosciences and Medicines》2024年第8期230-243,共14页生物科学与医学（英文）

摘　　要：Background: Vonoprazan fumarate, a novel potassium-competitive acid blocker, outperforms traditional proton pump inhibitors in acid suppression and can be effectively combined with antibiotics to eradicate Helicobacter pylori. Objective: The study aimed to determine if two Vonoprazan formulations—Vonoprazan Fumarate 20 mg Tablet of Beximco Pharmaceuticals Limited, Bangladesh (test product) and Takecab 20 mg Tablet of Takeda Pharmaceutical Company Limited, Japan (reference product)—met FDA’s bioequivalence requirements by comparing their pharmacokinetic characteristics in healthy Bangladeshi adults. Methods: This was a single-center, randomized, open-label, two-period, two-sequence, laboratory-blind, double-crossover experiment. After 10 hours of fasting, 18 subjects were randomly assigned to receive a single oral dose of either formulation. During each treatment period, blood samples were collected at specific times (pre-dose and up to 48 hours post-dose) to measure plasma Vonoprazan levels using liquid chromatography-tandem mass spectrometry. A non-compartmental model was used to calculate pharmacokinetic parameters using the plasma drug concentration-time profile. A statistical comparison of the pharmacokinetic parameters of the two formulations of the test and reference product was conducted using SAS® statistical software to assess the bioequivalence. Primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) and secondary parameters (Tmax, T1/2, Kel, and AUC extrapolation) were calculated for both drug formulations. If the confidence intervals for the natural log-transformed Cmax, AUC0-t, and AUC0-∞ values fell between 80% and 125%, the drug products would be considered bioequivalent. Result: The geometric mean ratio of Vonoprazan between the test and reference groups was found to be 109.04% (99.47% - 119.53%), 101.37% (95.58% - 107.50%), and 101.24% (95.43% - 107.41%), with 90% confidence intervals (CIs) for the Cmax, AUC0–t, and AUC0–∞, and these outcomes met the regulatory requirementsBackground: Vonoprazan fumarate, a novel potassium-competitive acid blocker, outperforms traditional proton pump inhibitors in acid suppression and can be effectively combined with antibiotics to eradicate Helicobacter pylori. Objective: The study aimed to determine if two Vonoprazan formulations—Vonoprazan Fumarate 20 mg Tablet of Beximco Pharmaceuticals Limited, Bangladesh (test product) and Takecab 20 mg Tablet of Takeda Pharmaceutical Company Limited, Japan (reference product)—met FDA’s bioequivalence requirements by comparing their pharmacokinetic characteristics in healthy Bangladeshi adults. Methods: This was a single-center, randomized, open-label, two-period, two-sequence, laboratory-blind, double-crossover experiment. After 10 hours of fasting, 18 subjects were randomly assigned to receive a single oral dose of either formulation. During each treatment period, blood samples were collected at specific times (pre-dose and up to 48 hours post-dose) to measure plasma Vonoprazan levels using liquid chromatography-tandem mass spectrometry. A non-compartmental model was used to calculate pharmacokinetic parameters using the plasma drug concentration-time profile. A statistical comparison of the pharmacokinetic parameters of the two formulations of the test and reference product was conducted using SAS® statistical software to assess the bioequivalence. Primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) and secondary parameters (Tmax, T1/2, Kel, and AUC extrapolation) were calculated for both drug formulations. If the confidence intervals for the natural log-transformed Cmax, AUC0-t, and AUC0-∞ values fell between 80% and 125%, the drug products would be considered bioequivalent. Result: The geometric mean ratio of Vonoprazan between the test and reference groups was found to be 109.04% (99.47% - 119.53%), 101.37% (95.58% - 107.50%), and 101.24% (95.43% - 107.41%), with 90% confidence intervals (CIs) for the Cmax, AUC0–t, and AUC0–∞, and these outcomes met the regulatory requirements

关 键 词：BIOEQUIVALENCE Vonoprazan Pharmacokinetics 

分 类 号：R96[医药卫生—药理学]