<p>Pharmacokinetics and Bioequivalence of Two Formulations of Valsartan 80 mg Capsules: A Randomized, Single Dose, 4-Period Crossover Study in Healthy Chinese Volunteers Under Fasting and Fed Conditions</p>

Abstract

Purpose: To compare the bioequivalence of two formulations of valsartan (80 mg capsules) under fasting and fed conditions in healthy Chinese volunteers using a full-replicate study design. Methods: A total of 78 Subjects were randomly assigned to fasting cohort (n = 48) or fed cohort (n = 30). Each cohort includes 4 single-dose observation periods and 3-day washout periods. Blood samples were collected at designed time point. Plasma concentration of valsartan was analyzed by a validated LC-MS/MS method. Noncompartmental analysis method was employed to determine the pharmacokinetic parameters. Based on the withinsubject standard deviation (S WR) of the reference formulation, either reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was used to evaluate the bioequivalence of the two formulations. Results: Under fasting conditions, the RSABE method was used to evaluate the bioequivalence of C max (S WR >0.294), while ABE method was used to evaluate the bioequivalence of AUC 0-t and AUC 0-∞. The geometric mean ratio (GMR) of the test/reference for C max was 99.52%, and the 95% upper confidence bound was <0. For AUC 0-t and AUC 0-∞ comparisons, GMRs were 102.07% and 101.92%, and the 90% CIs of the test/reference were 96.28%-108.21%, 96.28%-107.88%, respectively. Under fed conditions, the S WR value of C max , AUC 0-t and AUC 0-∞ all exceeded the cutoff value of 0.294 and therefore, the RSABE method was used. The GMRs for C max , AUC 0-t and AUC 0-∞ were 98.78%, 103.33% and 103.08%, respectively, while the 95% upper confidence bound values were all <0. These results all met the bioequivalence criteria for highly variable drugs. All adverse events were mild and transient. Conclusion: In this study, the generic formulation of valsartan 80 mg capsule was considered to be bioequivalent to the reference product under both fasting and fed conditions, and satisfied the requirements for marketing in China. NMPA Registration No: CTR20181422.

A validated LC–MS/MS method for analysis of Cabergoline in human plasma with its implementation in a bioequivalent study: investigation of method greenness

“…LC/MS/MS is a commonly used method in bioequivalence studies [27][28][29][30][31][32][33] for drugs detection in the plasma because of the high accuracy and sensitivity of the mass detector. Additionally, mass spectrophotometric detector is preferred over the UV and Refractive index (RI) detectors in terms of sensitivity as it measures in nano-scale levels [34,35].…”

Pharmacokinetics, Bioequivalence and Safety of Cloperastine in Chinese Healthy Subjects Under Fasting and Postprandial Conditions

“…In addition, an appropriate gender ratio was also considered in this trial. However, it was generally recognised that the gender imbalances in previous BE studies were due to the provisions on gender ratio in BE research lacking international unified standards [17,18]. In some countries, BE clinical trials do not include female subjects, while the guidelines for BE clinical trials in China require an appropriate proportion of female subjects.…”

Comparative Pharmacokinetics Between a Fixed‐Dose Combination of Pitavastatin/Valsartan 4/160 mg and the Corresponding Individual Components Through a Partial Replicated Crossover Design in Healthy Male Subjects

“…Only about 20% of valsartan is recovered as metabolites, and cytochrome P450 isozymes are known to contribute little to its metabolism 15 . In a previous study, the intraindividual CV% of the C max of valsartan was 39%, which considers valsartan as a highly variable drug (HVD) because it is larger than 30% 16 . Therefore, the bioequivalence of valsartan for C max can be evaluated by the scaled bioequivalence criteria according to several regulatory guidelines as an HVD.…”

“…15 In a previous study, the intraindividual CV% of the C max of valsartan was 39%, which considers valsartan as a highly variable drug (HVD) because it is larger than 30%. 16 Therefore, the bioequivalence of valsartan for C max can be evaluated by the scaled bioequivalence criteria according to several regulatory guidelines as an HVD. The approved dosages are 1, 2, and 4 mg once daily for pitavastatin, and 80 to 320 mg once daily for valsartan.…”