Pharmacokinetic aspects of the sublingual administration of vincamine.

The sublingual absorption of vincamine used as tracer occurs in two successive absorption steps: true sublingual absorption and absorption in the gastrointestinal tract of the drug dissolved in the saliva and not absorbed through the buccal mucosa. This is confirmed by a pharmacokinetic study and simulation. These two successive absorptions can explain the increase in the amounts of drug absorbed.

Effect of cigarette smoking on mexiletine kinetics.

The effect of cigarette smoking on the kinetics of a single, 200 mg, oral dose of the antiarrhythmic drug mexiletine was investigated in healthy subjects. Cigarette smoking had no effect on absorption or distribution of the drug, but it significantly reduced the elimination t1/2 from 11.1 +/- 3.4 to 7.2 +/- 1.8 hours; the effect on clearance was less significant. Determination of the urinary concentrations of the three major metabolites of mexiletine (mexiletine glucuronide conjugate, hydroxymethylmexiletine, and p-hydroxymexiletine) indicated that cigarette smoking selectively induced conjugation of mexiletine with glucuronic acid as well as aliphatic hydroxylation to yield hydroxymethylmexiletine, but that it had no effect on the formation of p-hydroxymexiletine.

Proteases during the growth of Ehrlich ascites tumor. II. The kallikrein-kinin system.

Ascitic fluid and ascites tumor cells from Swiss mice bearing Ehrlich ascites tumor were assayed for components of the kallikrein-kinin system at various times during tumor growth. Changes in component levels were correlated with those in the plasma. Ascitic fluid contained an acetone-activated prekallikrein that increased in concentration during tumor growth and reached peak levels during the 7th-10th day post transplant. No free kinin activity was present in the ascitic fluid. During tumor growth, kininogen levels increased in parallel with prekallikrein levels. The ascitic fluid also contained a kinin-destroying activity that was initially high during the early phase of tumor growth. Tumor cell fractions, prepared by ultracentrifugal techniques, had no kinin-forming activity while possessing kinin-destroying activity that was localized in the soluble protoplasmic protein and nuclear fractions. The kinin-forming activity of the ascitic fluid resembled that of the plasma with respect to pH optima, kinetics of kinin formation, and effect of protease inhibitors. The kininase activity of both ascitic fluid and plasma differed from that of the tumor cell fractions.

Proteases during the growth of Ehrlich ascites tumor. I. The fibrinolysin system.

Component levels of the fibrinolysin system in the plasma and ascitic fluid of Swiss mice bearing Ehrlich ascites tumor cells were determined during a 15-day tumor growth time phase. During tumor growth, the concentration of plasminogen in the ascitic fluid decreased inversely to the total packed cell volume. Free plasmin was not present in the ascitic fluid nor was there any measurable plasminogen activator activity. Both antiplasmin activity and fibrinogen levels present in the fluid decreased during tumor growth. The nuclear and mitochondrial-microsomal subcellular fractions of the tumor cell exhibited plasminogen activator activity. No significant changes in the above parameters occurred in the plasma during the tumor growth period we studied.