Biomedical subjects

B Vrhovac

Publications and source records attributed to B Vrhovac.

At least 19 recordsLinked to original sources

PubMed1999

How long can an escalation of dose override tolerance to the hypotensive efficacy of nitroglycerin infusion in coronary care patients.

Tolerance to nitroglycerin infusion (NG) can be overridden by dose escalation. The aim of this study was to define for how long it can be done for hypotensive efficacy of NG, in a coronary care setting. A prospective trial with an intra-individual therapeutic comparison was performed in 60 patients with acute myocardial infarction or unstable angina. Initial efficacy of NG was confirmed by a 10% blood pressure decrease (measured by cuff). Seventy-two-hour NG infusion was interrupted, for 30 minutes, every 12 hours. If blood pressure increased by 10% after infusion interruption, the infusion was continued at the previous rate. If blood pressure did not increase (detected tolerance--weakened efficacy of NG), the dose was increased until pressure decreased by 10% and the infusion was continued at the new dose. Failure to achieve hypotensive response, despite a 5-fold dose increase, indicated onset of resistance--completely lost hypotensive efficacy of NG. The majority of patients (49 out of 55) who developed tolerance, developed it during the first 36 hours, while the majority of those who developed resistance (33 out of 40), developed it within 60 hours of the infusion. Tolerance was overridden by dose escalation in 41 out of 55 patients, which was repeated in 31 patients. Complete restoration of NG action was possible over 24 hours in half the patients, and over 48 hours in one third of the patients. Three out of 34 patients who developed tolerance before the 13th hour did not develop resistance during the following 60 hours of dose up-titration. The conclusion is that tolerance to NG can be overridden by dose escalation in the majority of patients for a significant period of time, which is useful in clinical practice.

Aged↗

PubMed1998

Variations in the risk of gastrointestinal hemorrhage with non-steroidal anti-inflammatory drugs and localization of lesions.

The aim of this prospective study was to determine the effect of ulcerogenic drugs in patients with bleeding peptic ulcers and erosions with respect to their age and sex, ulcer history and additional risk factors such as family medical history, alcohol use, smoking, coffee consumption and stress. Of 367 patients with bleeding gastroduodenal lesions admitted during a period of 15 months, 88 (24%) had previously received ulcerogenic drugs. The most frequently taken drugs were aspirin (44.3%), piroxicam (12.3%) and ibuprofen (7.4%). Bleeding lesions were 1.4 times more frequently found in male users than in female users, and 2.1 times more often in male unusers. Males were more commonly receiving drugs than females (59.8%:40.2%), particularly those aged 34 to 54 years. Forty (45.5%) users had previously suffered from ulcer disease, 48 (54.5%) had negative history. There was no additional risk factor in 48%, whereas 58% of the users had one or more risk factors. It may be concluded with great certainty that NSAIDs caused hemorrhage in 13% of all admissions. Among users, a total of 119 different gastric and duodenal lesions were found. Gastric lesions were more common (54%) than duodenal lesions (46%) in males, while in females an inverse ratio was observed (41% of gastric and 59% of duodenal lesions). Among nonusers, gastric lesions were more frequent in females (M:F, 42%:48%), and duodenal lesions in males (M:F, 58%:52%). The number of lesions increased with age in both users and nonusers. Forty-three percent of all drug users had ulcers in the prepyloric region, 23% on the lesser curvature, and 14% at the posterior wall of the gastric corpus. Gastroduodenal erosions were seen in 11% of the males and 1% of the females. In nonusers, ulcers were found on the posterior wall of the corpus (27%), on the lesser curvature (25%) and in the prepyloric region (24%). Bleeding gastroduodenal erosions were found in 4% of the patients. Distribution of bleeding duodenal ulcers was similar in drug users and in nonusers, i.e. anterior wall (45%:44%), posterior wall (28%:27%), lower wall (16%:16%) and upper wall (3%:4%) of the duodenum. NSAIDs had no influence on the localization of duodenal ulcers. In this study, there was no death from ulcer disease with NSAID use. It may be concluded that NSAIDs are a common cause of damage to gastroduodenal mucosa. The risk of drug therapy should be balanced against the risk of the disease.

Adult↗

PubMed1997

Problems with drugs in Croatia.

Croatia has 4.8 million inhabitants, 11,800 physicians, 2000 pharmacists, two now shareholding, pharmaceutical companies (about 6500 employees, total sales of about 350 million US dollars). There are a number of problems due to the war (GNP fell from 3800 to about 1500 US dollars), occupation of 25% of its territory, 0.5 million refugees and lack of resources (139 US dollars/capita for health, about 40 US dollars i.e. 30%!! for drugs)--about three times less than before the aggression. The drug situation is controlled with the help of: (1) donations (approximate value of 600 million US dollars since 1991 from Europe and US), (2) (essential) drug formularies--250 for outpatients, and 580 generic names for various levels of hospital use, (3) special efforts to purchase drugs of good quality at a reasonable price (a kind of tender), (4) control of prescribing (prescriptions, specialists referral) especially by GPs. A new Medicines Act is in preparation and about 1000 generic names are on the market. DRUG EDUCATION: Pharmaca: the Croatian journal of pharmacotherapy has been published since 1962, there are several Drug bulletins (one published since 1975); special chapters on clinical pharmacology in textbooks, translation of three editions of Laurence's textbook with special commentary and adaptation to local needs; ADR spontaneous and intensive monitoring (WHO programme) with a personal feedback to the reporters and regular articles on drug use in a number of periodicals. Data on drug consumption indicates that there is room for improvement of prescribing. There is an enthusiasm for 'vasoactive drugs'--after dipirydamole came oxpentifylline and antimicrobials are always overprescribed. All these problems will hopefully decrease when the war finally stops and when industry (especially tourism) starts being fruitful again. In any case the importance of teaching of pharmacotherapy at the under- and postgraduate level should be recognized.

Journal Article↗

PubMed1996

Determination of bioequivalence of two furosemide preparations; the effect of high doses of furosemide on some pharmacokinetic parameters.

The bioequivalence of two oral preparations of the diuretic furosemide, namely (i) a Croatian pharmaceutical product (test preparation A) and (ii) a reference preparation B, both in a dose of 500 mg was assessed in an open, cross-over, randomized trial in 15 healthy male volunteers, in whom the HPLC method with a fluorescent detector was used to determine its concentrations. The test preparation (A) was found to achieve a considerably higher concentration (17.2 +/- 9.304 mg/l) than the reference preparation (11.1 +/- 6.484 mg/l); the time to peak concentrations was statistically significantly shorter for the test preparation (1.033 +/- 0.743 h) than for the reference preparation (1.656 +/- 0.586), and the areas under the concentration curves were statistically significantly greater for the examined preparation (65.9 mg.h/l) than for the reference preparation (46.845 mg.h/l). The relative bioavailability of the test preparation was 129%, i.e. it was not bioequivalent with the reference preparation. This finding was consistent with the previously performed laboratory quality testing in vitro, where the release of the reference preparation was found to be considerably slower and weaker than that of the test preparation. High doses of furosemide exemplified by 500 mg were found to affect only some of the pharmacokinetic parameters, i.e. they induce an accelerated absorption, an increase in serum concentration, and a prolongation of its half-life.

Adult↗

PubMed1995

Pharmacokinetic changes in patients with oedema.

The pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged. Binding of furosemide to plasma proteins is lower in patients with congestive heart failure (CHF), decompensated liver cirrhosis (DLC) and nephrotic syndrome, probably as a result of hypoalbuminaemia. The elimination half-life (t1/2) can be unchanged (CHF, DLC) or prolonged (chronic renal failure: CRF). Plasma and renal clearance are reduced in patients with CRF and nephrotic syndrome, but are almost unchanged in CHF and DLC. Disease-induced disorders are mainly responsible for the alterations of furosemide pharmacokinetics in oedematous conditions, while the influence of oedema per se is probably not clinically relevant. The pharmacokinetics of digoxin have been studied in a small number of studies only. In patients with CHF, considerable interindividual differences have been found. Because digoxin has a narrow therapeutic window, this drug should be administered cautiously to oedematous patients. Theophylline has higher bioavailability in patients with oedema, with a significantly higher Cmax in patients with hepatic cirrhosis and CHF than in healthy volunteers (29 and 22%, respectively). Furthermore, clearance decreases and t1/2 increases in these patients. Angiotensin converting enzyme (ACE) inhibitors are often administered as prodrugs, and their pharmacokinetic profile could be influenced by the diseases that accompany oedematous states. However, the effect of oedema is difficult to discriminate from that of the disease. Individual ACE inhibitors are affected differently, but importantly the dosage of perindopril should be reduced in patients with CHF, while for most other ACE inhibitors the changes in pharmacokinetic parameters are clinically irrelevant. In conclusion, studies on pharmacokinetic changes in oedema are limited. Besides affecting absorption (after oral administration) and conversion of the prodrug to the active form, probably as a result of the associated disease, oedema has not been proven to cause any clinically relevant changes in pharmacokinetic parameters for individual drugs. However, further studies of this aspect of pharmacokinetics are needed.

Edema↗

PubMed1995

Bioequivalence of two oral cyclosporine preparations.

A comparison of bioequivalence of two cyclosporine (CAS 59865-13-3) preparations was performed. Ten cyclosporine treated patients with transplanted kidneys were included. Criteria were successful transplantation and minimum period from transplantation of at least 6 months. Two months before the experiment, cyclosporine concentrations had to be in therapeutic range without significant oscillation, and kidney function stabile. There had to be no signs of cyclosporine nephrotoxicity. During the objective biochemical analysis it was not allowed to find malfunction in any of the patient's organ important for cyclosporine pharmacokinetics. Cyclosporine concentrations in whole blood were measured with a specific fluoroimmunoassay. Cyclosporine and metabolites concentrations were measured with radioimmunoassay with non-specific antibody. Mean value and standard deviations and shape of distribution were calculated for all numeric data of patients, measured biochemical and other laboratory parameters. Variance analysis for all measured cyclosporine concentrations according to sampling times (C0 to C12, maximal concentrations C(M), time to maximal concentrations t(M), times of absorption delaying t(Lag) and area under the measured concentration curves (AUC) were statistically checked. According to these data it is concluded that the preparations are bioequivalent; a time to reach maximum concentration was slightly shorter for test preparation (2.5 and 3.2 h, respectively), but not statistically significant. There are no significant differences between the areas under the concentration curves (1667 and 1665 ng.h/ml, respectively). After the calculation of pharmacokinetic parameters of concentration data measured by a non-specific method a significant difference for areas under concentration curves was seen (3709 and 4600 ng.h/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Adverse drug reactions resulting in hospital admission.

A 14-month (1992/3) prospective study was performed in two departments of the University Hospital Centre (UHC) in Zagreb. The aim of the study was to assess the rate of drug-related hospitalizations, drugs that caused adverse drug reactions (ADRs), and all factors which could have been of importance for their appearance. One hundred and thirty (2.5%) of 5,227 patients were admitted to hospital because of ADRs. The most frequently ADR-related drugs were nonsteroidal anti-inflammatory drugs and analgesics (64.6%). They were followed by cardiovascular agents (20.8%) and antimicrobials (3.8%). Acetylsalicylic acid (aspirin) caused 38.5% of hospital admissions, other nonsteroidal anti-inflammatory drugs (NSAIDs) 23.1% and medigoxin 15.4% of hospitalizations. The most frequent ADRs were upper gastro-intestinal tract bleeding (64.6%), cardiac rhythm disturbances (13.9%), blood cell disorders (4.6%) and hypoglycemia (2.3%). Regarding the patients' age, 52.3% of patients was younger and 47.7% older than 65. Sixty-one point five percent of patients was taking more than one drug, older patients (48 patients--77.4%) have been taking a significantly higher number of drugs than the younger (32 patients--47.1%) (p < 0.0001) ones. Drug interactions caused 23.8% of ADRs. Only 11 (8.5%) of patients suspected themselves that the drug might have caused the ADR. Improvement was observed in the majority of patients (65.4%), 25.4% recovered completely, 4 (3.0%) died in the hospital because of ADRs. 3.0% of patients as well died of their underlying diseases, 2.3% were transferred to other departments for their underlying diseases, and one patient left the hospital on his free will.

Adolescent↗

PubMed1993

Qualitative analysis of drug prescription in a geriatric population sample.

The rationality of specialist drug prescription in 154 patients older than 64 in 3 Zagreb homes for the aged was analyzed over an 11-month period. Categories analyzed were: number of prescribed drugs, justification of prescription, adequacy of the dose, route, form and therapy duration of the prescribed drugs, adequacy of the type of the prescribed drugs in the advanced age and the presence of contraindications of drugs used. The criterion of the rational drug use was the WHO's modified definition of rational drug therapy: "Application of an appropriate drug by a correct route in an adequate dose over a sufficiently long period of time". This basic criterion was further elaborated in relation to the analyzed categories. There were 2.66 (+/- 1.65) prescribed drugs per visit in which drugs were prescribed. In all analyzed categories, distinctive aberrations from the principles of rational drug prescription were found. One hundred and sixty-four (41.4%) of all drugs were unjustifiably prescribed and 103 (26.4%) were not dosed correctly. The duration of the therapy was inadequate for 60 (15.4%), route for 41 (10.5%), form for 32 (8.2%) of drugs prescribed. Seventy-five (19.3%) were not adequate because of patients' age and 15 (3.9%) were prescribed in spite of existing contraindications.

Aged↗

PubMed1993

Clinical pharmacology in Eastern European countries.

The current status of clinical pharmacology (CP) in the countries of the former Eastern block is presented. The difficulties in obtaining an accurate comparative view are pointed out. CP is unevenly developed in Eastern European countries and the number of hours devoted to basic/clinical pharmacology differs considerably 100/nil to 240/50. The same is true for the orientation of clinical pharmacology, where present. It is mainly basic in only a few countries (Rumania, Turkey, some parts of the former Yugoslavia) and mainly clinical in Czecho-Slovakia, Croatia, Hungary, Poland, Greece. The number of CP units and CP specialists varies greatly as well (from none to more than 10 per country). The awareness that CP, in many countries is still young and the branch of (clinical) medicine is of great importance, not only for rational pharmacotherapy but also for other services as well, education and research is growing. In spite of the fact that the present status of CP in Eastern European countries is generally unsatisfactory, there are realistic chances that in the (near?) future, CP will develop to match the activities now present in the more developed countries.

Bosnia and Herzegovina↗

PubMed1993

A dynamical model for the separation of secondary resistance from tolerance to nitroglycerin infusion.

A dynamic model for the estimation of a residual hypotensive efficacy of nitroglycerin (NG) infusion was constructed to distinguish secondary resistance from tolerance to NG, as lost vs weakened efficiency. The model was tested by individual comparison in 82 of 92 patients with acute myocardial infarction or unstable angina. Ten patients were excluded from the study protocol due to complications that required therapy modification. NG infusion (20 micrograms/ml) efficiency was initially confirmed by a 10% decrease in the mean brachial artery (cuff) blood pressure. The infusion (63 hours mean duration) was discontinued every 12 hours for 30 minutes and pressure changes were analyzed. If NG hypotensive efficacy was maintained (as proved by at least 10% pressure increase), infusion was carried on using the initial dose. Lack of 10% pressure increase after 30-minute infusion discontinuity (tolerance) indicated the need for an increase in the NG dose until 10% pressure decrease (not below 105/60) was obtained. Lack of 10% pressure decrease, with a 5-fold increase in NG dose (up to 320 micrograms/ml), was considered to be a sign of secondary resistance. There were no proceeding complications and tolerance was found in 72 patients. Beside tolerance, secondary resistance was simultaneously present in 16 patients, while the NG efficacy was restored by dose increase in the remaining 78% of tolerant patients. "Paradoxical" pressure decrease was noted in 12 tolerant patients after the infusion interruption, while "paradoxical" pressure increase was observed in 3 resistant patients during the infusion acceleration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Pharmacokinetics and interactions of digoxin, theophylline and furosemide in diseases with edema.

In diseases with generalized edema caused by decompensated heart and liver diseases or kidney failure digitalis preparations, diuretics and theophylline -- if lung disease accompanies one of the above states -- are often used. Literature dealing with theophylline, digoxin and furosemide pharmacokinetics in edematous diseases was analyzed as well as theophylline or digoxin interactions with furosemide. The results obtained in these investigations are very dissimilar, even contradictory. In all the drugs investigated, it was found that serum drug concentration was reduced, that there were no changes in comparison with non-edematous diseases and that drug concentrations were elevated in edematous diseases. Many problems in this field remain unsolved requiring further investigations of digoxin, theophylline and furosemide pharmacokinetics in liver, heart and kidney diseases accompanied by edema. As these drugs are often administered in these states, and having in mind their narrow therapeutic range (digoxin, theophylline), intoxication or a drug concentration decrease below the possibility of inducing any therapeutic effect are possible.

Digoxin↗

PubMed1991

Prophylactic administration of ranitidine after sclerotherapy of esophageal varices.

The present trial was carried out to determine the usefulness of H2-receptor antagonist drug therapy for the prevention of esophageal bleeding and esophageal varices in patients who underwent sclerotherapy. According to randomization, out of the 58 patients, 28 received, along with the usual standard therapy, ranitidine and 30 received placebo. Ranitidine, 50 mg, was administered intravenously over a period of 3 days every 8 hours, and then 150 mg of ranitidine was given per os in the evening for one month. For improvement of hemostasis and during the elective sclerotherapies, 1% polidocanol was used as the sclerosant. During each puncture, 2 ml was injected. Injections were paravasal and intravasal. After sclerotherapy, endoscopic examinations were carried out on the third day and one month later. Necrosis was noted in 42% of the patients and esophageal mucosal inflammation in 26%. Esophageal ulcers did not occur. There was no statistically significant difference between the two groups in terms of age, sex ratio, cause of liver cirrhosis, and the Child's classification. The size of the esophageal varices had no effect on the development of esophageal mucosal changes in correlation with the quantity of sclerosant. The comparison of the two groups of patients, sclerosed for hemorrhage and sclerosed electively, showed no statistically significant difference regarding esophageal mucosal changes. No differences between the ranitidine and placebo groups of patients were observed in this indication. It can be concluded that esophageal mucosal changes probably arise as a consequence of the sclerosant, its concentration, quantity and mode of application.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1990

Double-blind placebo controlled clinical trial of almitrine bismesylate in patients with chronic respiratory insufficiency.

The efficacy and safety of almitrine bismesylate, a new respiratory stimulant, in patients with the hypoxaemic form of chronic respiratory insufficiency caused by chronic bronchitis and emphysema has been assessed. The multicentre trial of 12 weeks duration was double-blind and placebo controlled, with individual and group comparisons. Twenty three patients received almitrine 50 mg b.d. p.o. and 17 took placebo. In the almitrine group a significant increase in PaO2 was achieved (control value 54.4 mm Hg, rising to 59.1 mm Hg after 6 weeks, and to 59.4 mm Hg after 12 weeks). There was also a significant decrease in PaCO2 in the almitrine group after 12 weeks. No correlation was found between the plasma almitrine concentration, PaO2 and PaCO2. Lung function (FVC, FEV1, FEV1/FVC, Raw, TLC, RV, FRC) did not change in either group, but the degree of dyspnoea and performance in the 6 min walking test were significantly improved in the almitrine group. Adverse reactions appeared in 6 out of 23 patients on almitrine bismesylate (headache, urticaria, breathlessness, diarrhoea, chest pain, nausea and vomiting), causing drop out of 4 patients. Thus, almitrine bismesylate can be considered useful in the treatment of patients with chronic respiratory insufficiency.

Adult↗

PubMed1990

[Use of recombinant erythropoietin on secondary anemia in patients in the terminal phase of renal insufficiency on hemodialysis].

A group of 6 patients with a history of end-stage renal insufficiency on hemodialysis was receiving erythropoietin (EPO) in a dosage of 50 IU/kg body weight i. v. The hemogram values were followed regularly every week and the patients underwent other laboratory evaluations every month. At the beginning of the study, the number of erythrocytes amounted to 2.2 +/- 0.3 x 10(12)/l. After 4 weeks it was 2.3 +/- 0.4 (NS) (p = 0.001), after 8 weeks 2.8 +/- 0.4 (p = 0.007), and after 12 weeks 3.2 +/- 0.3. At the beginning, hemoglobin was 70 +/- 8 g/l, after 4 weeks 76.3 +/- 13.7 (NS), after 8 weeks 95.7 +/- 14.3 (p = 0.008), and after 12 weeks 102.2 +/- 12 (p = 0.001). The hematocrit value rose from 21.4 +/- 3.4 at the beginning of the study to 32.1 +/- 3.6 (p = 0.001) after 12 weeks. The trial showed no significant effect of EPO on serum potassium which amounted to 5.3 +/- 0.4 mmol/l at the beginning of the trial and 5.6 +/- 0.8 (NS) after 12 weeks; the rate of the rise of platelets from 132.8 +/- 2.4 x 10(9)/l to 155.2 +/- 42.2 was not significant either. The results demonstrate a marked improvement in the red blood cells of patients receiving EPO in the end-stage of renal insufficiency and its influence on their general condition. One female patient was excluded from the study participation because of a severe bone pain.

Adult↗

PubMed1989

Intensive monitoring of adverse drug reactions in infants and preschool children.

Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all 2359 children were examined. ADR were recorded in 63 children and were reported to the National ADR monitoring centre in Zagreb. Using the algorithm of Hutchinson et al. (1979), all ADR were classified as "definite", "probable", "possible" and "unlikely". Drugs were prescribed in 97.3% of children, 60.24% received an antimicrobial agent (43% of them on the basis of a sensitivity test), and an antipyretic was given to 1878 children, mostly paracetamol. ADR were most frequently caused by antibiotics (49 reactions to penicillin V, and 15 to amoxycillin) and secretolytics (7 reactions). ADR were followed by complete recovery and not a single child was hospitalized because of an ADR. The results, when compared with the very small number of broadly comparable studies, indicate that the incidence of ADR in this population is rather small and of minor importance.

Age Factors↗

PubMed1989

Controlled trial of the prophylactic administration of antibiotics in sclerotherapy of esophageal varices.

The aim of this controlled trial was to determine the usefulness of chemoprophylaxis in sclerotherapy of ruptured esophageal varices. Sixty patients bleeding from esophageal varices, without signs of infection at admission, were included in a randomized open trial of one-year duration. Thirty patients received, along with the usual standard therapy (infusions, transfusions) 4x1 g ampicillin intravenously over 3 days, and 30 patients received the standard therapy only. Bleeding varices of the esophagus were sclerosed transendoscopically intravenously using 1% polidocanol solution. Body temperature, general condition, white blood count, differential blood count and sedimentation rate were followed-up over three days. There were no statistically significant differences between the groups in the mean values of the mentioned parameters. There was no correlation between the dose of sclerosant used and body temperature or leukocyte count. Chemoprophylaxis proved to have no effect in this indication.

Adult↗

PubMed1989

A double-blind trial of ademetionine vs naproxen in activated gonarthrosis.

The efficacy and safety of ademetionine (A) vs naproxen (N) were tested in a double-blind trial carried out in 20 patients, each with activated gonarthrosis. The trial lasted 6 weeks. During the first week, A was administered at a daily dose of 3 x 400 mg and afterwards at a dose of 2 x 400 mg, whereas the daily dose of N during the first week was 3 x 250 mg and subsequently 2 x 250 mg. During the first two weeks, the patients were allowed to take paracetamol as an additional analgesic. The patients were examined at the beginning of the study and after 2, 4 and 6 weeks. The parameters tested were: pain (under different conditions), crepitation, joint swelling, circumference of joint, extent of motility and walking time over 10 meters. In addition to the usual laboratory tests, the serum keratane-sulphate concentrations (with monoclonal antibodies according to the ELISA technique of Eugene et al. [1985]) were also determined. At the end of the 6th week no statistically significant difference between the two patient groups treated was found; both groups exhibited a marked improvement on all parameters. At the end of medication, the keratane-sulphate concentrations were not significantly changed. Five patients under A and 3 under N reported gastrointestinal side effects which were possibly drug-related. This study, performed in a small number of patients, showed a good efficacy and safety of ademetionine. Only further studies on a larger scale will show the importance of ademetionine in the therapy of rheumatic diseases.

Adult↗

PubMed1987

Determination of biological equivalence of two atenolol preparations.

In healthy volunteers (n = 8), the biological equivalence of the two oral atenolol preparations was investigated. Atenolol concentration was assessed by HPLC. Drug and internal standard were isolated by adsorption with active charcoal. Chromatography was performed on RP-18 column (10 mu) with mobile phase of 0.015 mol/l KH2PO4/acetonitrile 70:30. The flow rate of the mobile phase was 1.5 ml/min. UV detector operated at the wave length of 225 nm. The sensitivity of the method was 25 micrograms/l and variation coefficients within the assay were less than 10% in the therapeutic concentration range. Biological half-life was on the average 3.8 h, absorption half-life 0.8 h, and the peak concentration time 2.5 h. Both preparations have been found bioequivalent.

Administration, Oral↗