Therapeutic monitoring of metipamide during antihypertensive therapy.

The aim of our study was to monitor metipamide during a two-month period of treatment and to determine whether the whole-blood levels estimated by high-performance liquid chromatography provide a relevant indicator of possible accumulation of the drug. We also analysed antihypertensive activity and biochemical changes in the blood of twenty hypertonic patients. The results of our clinical trial showed that metipamide is an effective first-line antihypertensive agent, in that it combines satisfactory reduction of blood pressure with a low frequency of side-effects and a simple once-daily dosage regime.

Study of the effect of Edikron on the immune system.

Using the nucleolar test, the authors investigated the effects of the new Czechoslovak cytostatic agent Edikron (gamma, gamma-bis[4-ethylphenyl]-alpha, beta-dibromisocrotonic acid] on Wistar rats. The test showed that Edikron, administered perorally in the dose of 100 mg/kg BW per day for 5 days, affects neither the number of leukocytes nor the proteosynthetic activity of peripheral lymphocytes. The serum levels of Edikron, assessed with the aid of HPLC method 90 min after its last administration, averaged 14.03 +/- 1.63 micrograms/ml serum. Histological examination of the spleen, lymph nodes and thymus of the experimental and control groups also failed to detect any changes. However, the administration of Edikron elicited a statistically significant rise of erythrocytes in the experimental group, but the reason for that has not so far been ascertained.

Pharmacokinetics of Damvar.

The pharmacokinetics of granulated Damvar (delta-(2-amino-6-hydroxy-3,4-dihydro-4-oxo-5-pyrimidinyl) valeric acid) after a single oral dose of 1000 mg was studied in 10 subjects with neoplastic disease. The rate of Damvar absorption from the digestive tract is not very fast. Maximal serum levels (13.5 micrograms/ml) were recorded 3 h after administration with minor interpersonal variations. The time course of Damvar serum concentrations coincides with its distribution in a two-compartmental pharmacokinetic model with biological half-life of 9.72 +/- 0.84 h. Only a small amount of Damvar is eliminated in urine during a period of 24 h (3.1% of the administered dose). Its renal clearance is also low (0.05 ml/s). The analysis of Damvar excretion in urine shows that kidneys play a minor role in its elimination from the body. Therefore the attention should be concentrated on the effect of Damvar administration in patients with disturbed metabolic functions.

[Binding of butocin to serum proteins (author's transl)]. / Die Bindung von Butocin an Serumeiweisskörper.

The binding of N-[-5-(6-purinylthio)-valeryl]-glycin ethylester (butocin, PVG) to serum proteins and pure human albumin was studied using the method of equilibrium dialysis. Its binding to protein in sera diluted 1:1 of 10 patients with malignant disease averaged 48.4 +/- 7.07%. At the butocin concentration of 20 micrograms/ml an average of 36% of butocin were bound to pure albumin. Only a small portion was bound to globulin fractions. Measurements of the saturation curve showed butocin to be bound to albumin molecule by one binding centre with a microscopic association constant kappa = 1.7 . 10(3) mol/l.

Clinical localization of tubular transport of exogenous substances exhibiting urine flow dependence excretion.

The proposed method is based on the assumption that a fluid flow dependent tubular transport process in the distal (diluting) segment of the nephron can be influenced by water diuresis as well as osmotic diuresis. If the fluid flow dependent transport process is localized in the proximal part of the nephron only, the urinary excretion of such a substance can be increased by proximal osmotic diuresis but not by water diuresis. By means of this method the localization of fluid flow dependent tubular transport processes of chloramphenicol and its metabolites (arylamines and total nitro compounds) has been studied in 17 healthy volunteers. The results indicate that the flow dependent transport processes of substances under study may be localized in the diluting segment.

The effects of functional adaptation of residual nephrons on the urinary excretion of drugs.

In patients with chronic renal failure due to glomerulonephritis, pyelonephritis or polycystic kidneys the urinary clearance of free chloramphenicol (C(CHL)) was depressed proportionally to GFR (C(In)). The ordinate intercept of the regression line of C(CHL) on C(In), however, consistently was positive (+3 to +5 ml/min). The fractional excretion of chloramphenicol in renal failure increased from its normal value of 50 percent as an exponential function of the decrease of GFR, and as a linear function of the fractional excretion of water or of sodium. Dietary sodium restriction had no influence on C(CHL) in the patients, while water diuresis, in normal subjects, enhanced the urinary excretion of chloramphenicol. The data suggest that chloramphenicol is reabsorbed by back-diffusion and that increases of the rate of flow of urine and tubular fluid prevent back-diffusion.