Improved method for quantitative analysis of vitamin K1i and vitamin K1 2,3-epoxide in human plasma by electron-capture gas-liquid capillary chromatography

Evidence for Impaired Hepatic Vitamin K1 Metabolism in Patients Treated with N-Methyl-Thiotetrazole Cephalosporins

SummaryIn 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin Ki was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause…

Quantitative analysis of vitamin K1 and vitamin K1 2,3-epoxide in plasma by electron-capture gas-liquid chromatography.

PLASMA CONCENTRATION-EFFECT RELATIONSHIP OF THE ANTIARRHYTHMIC AGENT LORCAINIDE

Lorcainide; II. Plasma concentration-effect relationship

Haemodynamic effects of a single intravenous dose of lorcainide in patients with heart disease

The cardiovascular effects of a single i.v. dose (2 mg/kg over 5 min) of lorcainide were studied in 14 patients with heart disease. In the haemodynamic part of the study (6 patients), the aortic and pulmonary systolic, diastolic and mean pressures, left ventricular systolic and end-diastolic pressures, cardiac output and the rate of rise of left ventricular pressure were measured before and for 30 min after administration of the drug. Lorcainide produced a slight and short-lasting decrease in the aortic and pulmonary systolic pressures, and all other pressure values remained unchanged. The cardiac output and systemic vascular resistance were not altered by lorcainide. It consistently depres…

Possible coumarin-like mechanism of action for cephalosporins.

In three patients treated with cephalosporins (one patient with latamoxef, two patients with cefazedone) vitamin K1 was injected to investigate whether this was followed by an increase in vitamin K1 2,3-epoxide plasma concentrations as compared to controls. Such a rise in K1-epoxide concentrations in the plasma can be demonstrated following treatment with coumarins. This reflects an inhibition of the vitamin K1-epoxide reductase in the liver. Coumarins are thought to induce hypoprothrombinaemia by such a mechanism. In all three patients we found a considerable increase in the vitamin K1-epoxide plasma concentrations following injection of 10 mg vitamin K1, whereas in normal subjects only tr…

SATURABLE PRESYSTEMIC ELIMINATION OF THE ANTIARRHYTHMIC DRUG LORCAINIDE

Klinische Pharmakologie II

1963 beschrieb Ommaya ein subkutanes Plastikreservoir, das nach Implantation unter die Kopfhaut einen direkten, sterilen, wiederholbaren Zugang zum Ventrikelliquor ermoglichte. Nach okzipitaler Bohrlochtrepanation des Schadels wurde ein Siliconkatheter in das Hinterhorn des Seitenventrikels eingefuhrt und an das Reservoir angeschlossen.

Lorcainide. I. Saturable presystemic elimination.