Disposition of vitamin K1 after intravenous and oral administration to subjects on phenprocoumon therapy

Article Details

Citation
Copy to clipboard

Øie S, Trenk D, Guentert TW, Mosberg H, Jähnchen E

Disposition of vitamin K1 after intravenous and oral administration to subjects on phenprocoumon therapy

International Journal of Pharmaceutics. 1988 Jun 15;48(1-3):223-230.

PubMed ID
Not Available
Abstract

The disposition and prothrombin-complex activity of a new i.v. dosage form of vitamin K1 using mixed micelles of glycocholic acid and lecithin as a vitamin K1 solution was studied in 9 volunteers on an oral phenprocoumon dosage regimen. Each of two volunteers received 10, 20, 40 or 60 mg i.v. and oral doses in a cross-over fashion. An additional subject received a single 60 mg i.v. bolus dose. The intravenous doses were well tolerated with no subjective or objective side-effects. Using a sensitive gas chromatographic assay (detection limit ≈ 5 ng/ml), the concentrations of vitamin K1 could be followed for 24–36 h after the i.v. doses and for 12–33 h after the oral dose. The steady-state apparent volume of distribution was 20±6 liters and the clearance was 70±19 ml/min. The bioavailability demonstrated large inter-individual variation ranging from 3.5% to 60%. After the i.v. dose, vitamin K1 showed multi-compartmental characteristics with a terminal half-life of 14±6 h. No dose dependency was detected in any of the pharmacokinetic parameters. The pharmacologic activity of vitamin K1 after i.v. and oral dosing, defined as the area under the curve of the increase in the prothrombin-complex activity over baseline values during phenprocoumon therapy, correlated well with the logarithmic value of the area under the plasma concentration-time of vitamin K1 (r2 = 0.677, t = 5.42, P < 0.001).

DrugBank Data that Cites this Article

Drugs