Search

An analytical method was worked out to determine Lonazolac in human plasma based on precipitation of human plasma with a precipitating agent and methanol. This deproteinized plasma was analyzed by liquid chromatography with the use of a reverse phase and fluorimetric detection. The described method is sufficiently sensitive (the limit of detection under 0.1 microgram/ml of plasma) and precise (error of the method = 9%). The precision of the method, recovery from the plasma (100 +/- 3%) and stability in frozen plasma (minimally one month) are presented. Application of the method in a comparison of the newly developed Czechoslovak preparation Lonazolac and the foreign preparation Irritren is shown. Results are documented by the course of the levels of both preparations in dependence on time and principal pharmacokinetic parameters derived from the one-compartmental model.

An inadequate efficiency of the fibrinolytic system was revealed in 50-60% of subjects suffering young age from venous thrombosis or myocardial infarction. In a group of 27 patients with the history of deep venous thrombosis of the idiopathic type the authors revealed a significant relationship between the elevated body weight and inadequate fibrinolysis manifested by a reduced fibrinolytic capacity and excess inhibitor of plasminogen activator and its inadequate decline after desmopressin infusion (DDAVP). In a group of 29 patients, who had suffered a myocardial infarction when young, the authors revealed a significant association between reduced fibrinolytic capacity and elevated body weight, hypertriglyceridaemia and increased immunoreactive insulin secretion after a glucose load. In half the investigated subjects it proved possible to improve the reduced fibrinolytic capacity by a low energy diet.

The authors assessed the oxidative phenotype type debrisochin/spartein in 97 healthy volunteers aged 23 to 56 years (45 men and 52 women). After metoprolol administration which served as a model substance, in doses of 100 mg p. o. at night, the authors collected urine during 8 hours. In the urine specimens they assessed by gas chromatography with detection of the electron capture (fig. 1) the metabolic ratio of metoprolol/alpha-hydroxymetoprolol (M/HM). The distribution of logM/HM on the frequency histogram was bimodal and made it possible to divide the group into extensive and poor metabolizers (fig. 2). The authors detected 6 poor metabolizers which corresponds to the results in the white population. The authors discuss the clinical impact of oxidative polymorphism in the treatment with metoprolol, diltiazem, quinidine and other drugs.

An analytical method of the assay of isosorbide dinitrate in the human plasma was developed. The analytical method is based on the extraction of the plasma with toluene and direct injection of the toluene phase on the packed column (3% SE 30) of a gas chromatographic apparatus. After separation, detection is carried out with a detector of electron capture. The reported method is rapid (period of analysis = 10 min), sensitive (limit of detection = 0.1 ng/ml of plasma) and sufficiently precise (error of the method, 12%). The precision of the method during the day and between days is presented. The application of the method is shown in a comparison of a Czechoslovak preparation in advance development with the foreign preparation Iso-Mack. The results after administration of 5 mg of the Czechoslovak and foreign sublingual form of the preparation in a group of ten volunteers are documented with the course of the levels in the individual experimental subjects and the principal pharmacokinetic derived from the one-compartmental model.

Quantitative studies were carried out of the in vitro and ex vivo effects of phenylbutazone and 3-oxoalkyl substituted diphenyldioxopyrazolidines (kebuzone, tribuzone, benzopyrazone) on platelet aggregation. The specified pyrazolidine derivatives exhibited in vitro inhibitory effects on secondary platelet aggregation (induced by adrenaline and collagen), commensurable with the effects of sulfinpyrazone. The ex vivo efficacy was markedly influenced by the height of the drug level in blood and by differences in the elimination kinetics of the pyrazolidine derivatives in human organism. Inhibitory activities against primary aggregation (induced by ADP and thrombin) were found in vitro mainly in the phenyloxoalkyl derivative of diphenyldioxopyrazolidine (benzopyrazone) and its analogues. By substitution on the phenyl attached to its alkyl side chain (for example, by a halogen in the meta position), compounds were obtained which also possessed higher activities inhibiting secondary platelet aggregation.

Restoration of the sinus rhythm in atrial fibrillation and flutter can be achieved by cardioversion, using an electric discharge, or by medicamentous treatment. Medicamentous treatment is based above all on a combination of antiarrhythmic drugs. By the concurrent administration of quinidine, verapamil and digoxin restoration of the sinus rhythm is achieved in 80% patients, on average after 37 hours at plasma quinidine levels of 2.57 +/- 1.4 (SD) micrograms/ml and digoxin levels of 1.90 +/- 1.3 (SD) nmol/l. Restoration of the sinus rhythm in atrial flutter calls for higher quinidine and digoxin levels than in atrial fibrillation (p less than 0.01). Prolonged persistence of the sinus rhythm during treatment with maintenance doses of quinidine, verapamil and digoxin is not satisfactory so far and after 12 months the sinus rhythm persists only in 30% of the patients where the rhythm was originally restored.

The fibrinolytic capacity was assessed in 18 healthy subjects and in 8 patients each with non-idiopathic venous thrombosis, idiopathic venous thrombosis and myocardial infarction after intravenous administration of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.4 microgram/kg) in comparison to venous occlusion. In healthy subjects the results obtained by either stimulus were approximately in agreement. Compared to the control group, in patients with non-idiopathic venous thrombosis the fibrinolytic capacity was not changed either after venous occlusion or after administration of DDAVP. In 5 out of 8 patients with idiopathic venous thrombosis the capacity was significantly reduced both after venous occlusion and after administration of DDAVP. In 4 out of 8 patients with myocardial infarction the capacity was significantly below the limit after administration of DDAVP while it was not after venous occlusion. In determining the fibrinolytic capacity DDAVP proved to be superior to venous occlusion.

Methods used in clinical and clinical pharmacological assessments of phlebotropic drugs are outlined. The knowledge of the pharmacokinetics and metabolism of phlebotropic drugs in human organism is far from complete as yet. Of objective methods proving haemodynamic effects of phlebotropic drugs, the authors have the best experiences with the strain-gauge type occlusive plethysmography, which is capable of proving a reduction of the capillary filtration fraction even after a single administration of an active preparation to healthy volunteers. The control of the patient's subjective complaints by phlebotropic drugs is documented by statistically significant findings in double-blind clinical trials with a placebo.

An analytical method was developed to determine nitroglycerin in human plasma. The analytical method is based on the extraction of plasma with hexane and the feeding of the packed collumn (10% OV 101) of the gas chromatographic apparatus with the concentrated hexane phase. After separation, detection is carried out by a detector of electron capture. The described method is sensitive (limit of detection = 50 pg/ml of plasma) and sufficiently precise (error of the method = 13%). The precision of the method during the day (+/- 12%) and between the days (+/- 8%) is presented, as well as the return of nitroglycerin from plasma (95%). An application of the method on comparing the pharmacokinetic parameters in two dosage forms used in Czechoslovakia is shown. The results after the administration of one mg of the sublingual and spray forms of nitroglycerin preparations are documented by the course of the levels in the individual experimental subjects and the principal pharmacokinetic parameters derived from the one-compartmental model.

The radioreceptor assay (RRA) was used to quantitate plasma triazolam concentrations in eight female volunteers following single 0.5 mg doses of two tablet formulations in a cross-over study. Bioavailability in terms of area under the plasma concentration versus time curve (AUC0 infinity), maximum plasma concentration (Cmax), time to maximum (tmax), and mean residence time (MRT) was not statistically significantly different from one formulation to the other.