Determination of pharmacokinetic parameters of vitamin K1 in rats after an intravenous infusion

Pharmacokinetic parameters of vitamin K1 have a large range of values in different literature. The aim of this study was to determine the pharmacokinetic parameters of vitamin K1 following post-constant speed intravenous infusion (PCSII) to provide rational pharmacokinetic parameters of vitamin K1 and compare these with results of noncompartmental analysis following intravenous injection (IV). After 15 hours intravenous infusion of vitamin K1 in rats, the logarithmic concentration–time curve of vitamin K1 was fit to a linear equation following PCSII (R² = 0.9599 ± 0.0096). Then, half-time (T_1/2), apparent volume of distribution (V_d), and clearance rate (CL) were estimated successively. T_1/2 of vitamin K1 was 4.07 ± 0.41 hour, CL was 89.47 ± 3.60 mL/h, and V_d was 525.38 ± 54.45 mL in rats following PCSII. There was no significant difference in pharmacokinetic parameters of vitamin K1 among different sampling times. For noncompartmental analysis, T_1/2 and mean residence time (MRT_INF) for a sampling duration of 6h were shorter than those of 12 hours or 24 hours sampling duration following IV (P < .05, P < .01). In addition, T_1/2 of vitamin K1 was obviously different from MRT-equated half-time (T_{1/2, MRT})(P < .05). V_d and CL of vitamin K1 following PCSII were larger than those following IV based on noncompartmental analysis (P < .01). The results demonstrated that drug distribution in the body was balanced and the Napierian logarithmic concentration–time curve of vitamin K1 fit to a linear equation following PCSII. Vitamin K1 has a long T_1/2 and a relatively large V_d following PCSII.