A randomized, open, two-period, cross-over, single oral dose, pharmacokinetics and bioequivalence study of vitamin K1 in healthy volunteers under fasting and fed conditions

Objective Vitamin K 1 (VK 1 ) supplementation is an important therapeutic agent for the treatment of hemorrhage due to VK 1 deficiency. It can be administered orally, intramuscularly, or via intravenous injection. This study was conducted to evaluate the bioequivalence of VK 1 micelle produced by Hainan Biotech Pharmaceutical Co., Ltd. compared to the original drug KONAKION®MM when administered orally. Methods This was a randomized, open-label, two-period, single-dose, crossover bioequivalence study conducted under both fasting and fed conditions, with 28 participants in each condition. Participants received 10 mg oral dose of test (T) or reference (R) drug in the first period and the opposite drug in the second period, with a 9-day washout. Blood concentrations of the E and Z isomers of VK 1 were measured at 26 or 29 time points for fasting condition or fed condition, respectively. Bioequivalence was determined if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the peak concentration (C max ), the area under the concentration-time curve from time zero to the last measurable concentration (AUC 0–t ) and the extrapolated area under the curve from time zero to infinity ( AUC 0 − ∞ ) after log transformation for VK 1 E isomer fell within the 80.00%–125.00% range under both fasting and fed conditions. The International Normalized Ratio (INR) was used as an exploratory endpoint to observe changes following dosing. Safety assessments included vital signs and electrocardiograms (ECGs). Results Under fasting conditions, the 90% CIs for the GMRs of C max , AUC 0-t , and AUC 0 − ∞ for the VK 1 E isomer were 99.17%–119.24%, 103.91%–121.13%, and 105.72%–122.77%, respectively. Under fed conditions, the corresponding 90% CIs were 83.56%–120.82%, 84.98%–124.63%, and 83.97%–124.32%. All values fell within the 80.00%–125.00% equivalence margin, confirming bioequivalence between the two formulations. There were no significant changes in INR. The safety profile was favorable, with no serious adverse events (SAEs) or grade 3 or higher adverse events (AEs) reported. Conclusion The VK 1 micelle produced by Hainan Brilliant Pharmaceutical Co., Ltd. is bioequivalent to the original drug KONAKION®MM, supporting its approval as a generic product by oral administration. It demonstrated good safety and tolerability in healthy Chinese subjects. Clinical Trial Registration http://www.chinadrugtrials.org.cn/index.html , identifier CTR20223408; https://www.chictr.org.cn/ , identifier ChiCTR2500096211.