A randomized, open-label, three-period, cross-over, single intravenous or intramuscular dose, pharmacokinetics and bioequivalence study of vitamin K1 in healthy adults.

This study aimed to evaluate the bioequivalence of Vitamin K1 (VK1) injection produced by Hainan Brilliant Pharmaceutical Co., Ltd. compared to the original drug KONAKION®MM via intravenous (IV) administration and to evaluate the pharmacokinetic (PK) characteristics and bioavailability of VK1 via intramuscular (IM) administration. A randomized, open-label, three-period, single-dose crossover study enrolled 34 subjects. Periods 1 and 2 involved a single 10 mg IV dose of test (T) or reference (R) formulation in crossover design, with a 9-day washout. In period 3, all received a 10 mg IM dose of T formulation. Blood concentrations of the E and Z isomers of VK1 were measured at 29 time points. Bioequivalence was determined if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the peak concentration (Cmax), the area under the concentration-time curve from time zero to the last measurable concentration (AUC0-t) and the extrapolated area under the curve from time zero to infinity (AUC0-∞) after log transformation for VK1 E isomer fell within the 80.00-125.00% based on the data of period 1 and 2. The data of the third period was only to recognize the PK characteristics of VK1 via intramuscular administration. Safety assessments included vital signs and electrocardiograms (ECGs). After 10 mg single dose of intravenous administration of test formulation and reference formulation, the GMRs of Cmax, AUC0-t, and AUC0-∞ for the VK1 E isomer were 96.79%, 106.45% and 106.54% (the 90% CIs were 92.32%-101.48%, 101.64%-111.49%, and 101.70%-111.61%, respectively). All values fell within the 80.00-125.00% equivalence margin, confirming bioequivalence between the two formulations. The bioavailability of intramuscular administration route was about 56%. Safety was favorable, with no serious adverse events (SAEs) or grade ≥ 3 AEs. The test VK1 injection is bioequivalent to KONAKION®MM when administered IV, supporting its generic approval, and demonstrated good safety in healthy Chinese subjects. Registry: chinadrugtrials.org, TRN: CTR20230319, Registration date: February 6, 2023.