[Unasyn in severe hospital infections]. / Unasyn u tezkých nemocnicních infekcí.

A total 16 patients with moderate and serious surgical and urogenital infections were treated intravenously with the Unasyn IM/IV inj., combination of ampicillin and sulbactam, which is a beta-lactamase inhibitor. In this combination, sulbactam saves the ampicillin against the effects of beta-lactamases and extends the susceptibility to ampicillin of previously ampicillin-resistant strains. Clinical cure was observed in 69% of the patients, improvement in 19%, and failure in 12%. Microbiological elimination was proved in 50% of the patients, persistence in 6%, a in the rest of the patients (44%) were microbiological response unevaluable. The evaluation of subjective and objective tolerance of Unasyn IM/IV inj. was excellent. It follows from this study that the combination of ampicillin with sulbactam can be considered an effective and safe treatment of nosocomial infections, especially in the departments with an increasing rate of ampicillin-resistant strains due to production of the beta-lactamases.

[Antibiotic prophylaxis of early infection in otorhinolaryngology surgery]. / K antibiotické profylaxi ranné infekce pri operacích v otorinolaryngologii.

The authors draw attention to the urgency of antibiotic prophylaxis of early infection in surgical disciplines and emphasize the main principles of its expedient implementation. In otorhinolaryngology antibiotic prophylaxis proves useful in a number of surgical procedures; the authors submit, however, also examples when they do not consider antibiotic prophylaxis expedient. Among antibiotics used for prophylactic administration they consider at present for the majority of ENT operations cephalosporins of the first generation most useful. Their spectrum is roughly equal to the action of penicillin, oxacillin and ampicillin combined. When selecting an antibiotic, however, always ain individual approach must be used and its selection must be adjusted to the epidemiological situation in different areas and health institutions. The prophylactic use of different types of antibiotics cannot have permanent validity, we have to foresee rotation of antibiotics and the introduction of further new preparations.

Pharmacokinetics and pharmacodynamics of conventional and controlled-release formulations of metipranolol in man.

The pharmacokinetics and beta-adrenoceptor blocking effects of conventional and sustained-release metipranolol have been studied in 6 healthy male volunteers given a single oral dose of 40 mg. Plasma drug concentrations determined by TLC and a radioreceptor assay, and the inhibition of exercise-induced tachycardia, were monitored for 48 h. Relevant amounts of active metabolites other than deacetylmetipranolol were not found. Compared to conventionally formulated metipranolol, the controlled-release product had a prolonged mean residence time (10.7 vs 5.5 h), the peak drug concentration was halved and the time to peak drug concentrations was delayed. Relatively constant plasma concentrations (cideal = 6.5 ng/ml) and a clinically significant reduction of exercise-induced tachycardia were maintained throughout a 24 h dosing interval. An individual deacetylmetipranolol plasma concentration-effect relationship was evaluated using the Emax model. Mean parameters were Emax 26% and C50 2.9 ng/ml.

Contribution of clinical pharmacology to a rational use of cardiac glycosides in Czechoslovakia.

In Czechoslovakia, drug utilization studies showed that oral forms of digoxin and lanatoside C are traditionally the most prescribed cardiac glycosides. Our study of the relative bioavailability of the oral form of lanatoside C revealed that the drug has a low and irregular bioavailability making use of this frequently prescribed drug non-rational. The above data definitely contributed to a sharp decrease in the use of the oral form of lanatoside C in our country, which is in agreement with consumption trends in other European countries. However, the use of only drug forms with a good bioavailability is one aspect of new approaches applied in pharmacotherapy with cardiac glycosides resulting in gradual decrease of their consumption as a pharmacological group. Clinical pharmacological evaluation of individual drug forms and postgraduate education in clinical pharmacology of cardiac glycosides contribute significantly--apart from other regulatory measures--to a more rational use of cardiac glycosides in Czechoslovakia.

Cardiovascular drugs in Czechoslovakia--registration and consumption data.

Data on registration and consumption of cardiovascular drugs in Czechoslovakia were sorted from the computerized Drug Information System (DIS) for a detailed analysis. Cardiovascular drugs (including antiarrhythmics, cardiac glycosides, diuretics, antihypertensive agents and vasodilators) represent at present 10% of all registered drugs in Czechoslovakia with an ever increasing trend over the last ten years. For economical analysis of consumption of cardiovascular drugs, three methodological approaches (expenditure figures, material units--number of packages and DDD (Defined Daily Dosis), as a technical unit of measurement) were chosen. In the period of 7 years (1980-1986) all three methodologies confirmed the increasing trend of cardiovascular drugs consumption in Czechoslovakia. However, an international comparison of consumption data between Czechoslovakia and Sweden revealed lower levels in Czechoslovakia in this respect.

Interspecies pharmacokinetic scaling of metazosin, a novel alpha-adrenergic antagonist.

Based on pharmacokinetic data from mice, rats, and rabbits, the prediction of pharmacokinetics of intravenous metazosin in man has been performed. The correlations were based upon allometric scaling of plasma clearance and the volume of distribution at steady-state. A one-compartment body model approximating clinical pharmacokinetics fits well the elimination phase of subsequently measured metazosin concentrations in volunteers. Fitting human pharmacokinetic data to allometric equations enabled us to superimpose pharmacokinetic curves from different species.

[Utilization of cardiac glycosides in Czechoslovakia--does it correspond to need?]. / Spotreba srdecních glykozidu v CSSR--odpovídá potrebe?

The data are given on the consumption of cardiac glycosides (CD) in the CSSR over the past 18 years (1970-1987). Consumption expressed in terms of defined daily doses (DDD) permitted to construct time series of the consumption of this group of pharmacotherapeutic agents as a whole as well as individual CG and to compare the data thus obtained with similar data from abroad. The results indicate that the consumption of CG as a whole culminated in Czechoslovakia in 1983 (27.6 DDD per a population of 1000 per day = 27.6 DDD/1000/d) and that there has been a slow decline ever since. Compared with foreign data, Czechoslovakia's quantitative consumption of CG is roughly between countries noted for traditionally high consumption (GDR 84.8 DDD/1000/d) and those with low consumption (Scandinavian countries with the exception of Sweden, about 10 DDD/1000/d). Unlike Czechoslovakia, however, all other countries with well established CG consumption have been exhibiting a relatively steep and lasting decline in CG consumption since the late 1970s. This reduction reflects modern trends of CG pharmacotherapy, especially stricted consideration of the uses as distinct from the risks of CG administration, as well as some of the recent efforts to terminate long-term CG treatment particularly in vaguely indicated cases. As for individual CG consumption, Czechoslovakia, similarly as other countries, has been favouring more rational prescription of oral digoxin at the expense of the oral form of lanatoside C, while parenteral digoxin has for all practical purposes become a substitute for strophantin.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of temocillin after intravenous and intramuscular administration.

Pharmacokinetics of temocillin (BRL 17421) was studied in a crossover study in 10 male healthy volunteers after administration 1 g of temocillin intravenously or intramuscularly. The mean serum levels of temocillin at the 5th min after i.v. administration were 131.57 mg/ml, at 1 h 71.27 mg/l and at 12.12 mg/l. The values of the pharmacokinetic parameters were as follows: AUC 509.2 mg X h X l-1, t1/2 4.2 h-1, Vd ss 11.57 l, Vd area 12.28 l, CL 2049 ml X h-1. The urinary excretion by 12 h was 70.58% of the administered dose of temocillin. The mean serum levels of temocillin after i. m. administration were at 2 h 46.65 mg/l and at 12 h 15.89 mg/l, the corresponding pharmacokinetic parameters were: AUC 501.38 mg X h X l-1, t1/2 4.3 h-1, Vd 12.69 l. The urinary excretion by 12 h was 57% of the administered dose of temocillin. It follows from the study that pharmacokinetic parameters of temocillin after both ways of temocillin administration are very closed and that the dose 1 g of temocillin is sufficient to create effective serum levels for the majority of sensitive gramnegative organismus.

Ontogenic drug studies in calves. I. Age dependent salicylate levels and metabolism.

Acetylsalicylic acid (ASA) was administered to 52 Friesian calves 1--60 days old by oral route in the field, 63.5 mg/kg body weight constantly between 9 and 10 a.m., i.e., 3--4 h after morning feeding. The animals were divided according to age into groups. Total salicylate levels, salicylic acid and salicyluric acid plasma levels were determined up to 6 h after administration. The older the animals, the lower were the total salicylate and salicylic acid levels and the higher the salicyluric acid levels. The age dependence is highly significant during the first two weeks of life. Glucuronides could not be detected in quantitatively measurable amounts.

Ontogenic drug studies in calves. II. Changes in salicylate levels and metabolism in calves with diarrhoea.

Acetylsalicylic acid (ASA) was administered by oral route to calves and mice. A comparison of plasma levels of salicylates and salicyluric acid was performed in healthy and diarrhoic calves. The calves were infected with E. coli enterotoxin producing strains. During the 6 h observation period increased levels of salicylates were found in all age groups of calves (1-60 days). There were no significant differences in salicyluric acid plasma levels between controls and diarrhoic animals. Intravenous injection of cholera toxin in mice caused lower levels of total salicylates, but increased levels of salicylic acid and salicyluric acid. The importance of adequate animal model is discussed.

Immunoglobulin levels in large calf agglomerations.

The zinc sulphate turbidity test was used to establish the total immunoglobulin levels of calves from birth to 4 months of age. Colostral immunity fell rapidly and the lowest levels were found in the third and fourth week of life. During the fifth week there was a significant increase. 25% of animals were hypogammaglobulinaemic in the first week of life. This ratio increased to 50% in the third week of life. At the age of two months the lowest immunoglobulin levels almost vanished. These findings are discussed as basic information for the appropriate management of calf agglomerations. Animals should be agglomerated only after the first months of life. When this is not possible, the pens for large agglomerations should have individual housing for the newly admitted calves. The importance of appropriate epizootological measures to reduce infections are pointed out.

Pregnancy interrupting effects of some bacterial toxins.

Embryotoxic properties of Shigella dysenteriae and Clostridium perfringens toxins, of E. coli endotoxin, V. cholerase and E. coli enterotoxins were compared in mice. E. coli endotoxin has embryotoxic effects at all stages of pregnancy. E. coli enterotoxin V. cholerae enterotoxin and Shigella dysenteriae toxin are most effective mainly at earlier stages of pregnancy. Clostridium perfringens toxin has no embryotoxic effect.

PIP: Pregnancy interrupting effects of some bacterial toxins were studied in mice. Embryotoxic properties of Shigella dysenteriae and Clostridium perfringens toxins, Escherichia coli endotoxin, Vibrio cholerae, and Escherichia coli interotoxins were compared up to Day 18 of pregnancy following injections on Day 6, 8, or 13 of pregnancy. Escherichia coli endotoxin caused embryotoxic effects in all stages of pregnancy while Escherichia coli enterotoxin, Vibrio cholerae enterotoxin, and Shigella dysenteriae toxin were most effective mainly at earlier stages of pregnancy. Histological studies revealed indirect embryotoxicity at later stages by placental damage. The main site of damage was the fetal side for Shigella dysenteriae toxin and the maternal side for Escherichia coli endotoxin, enterotoxin, and cholera toxin. Clostridium perfringens toxin had no embryonic effect.

Sexual differences in the metabolism of salicylates.

During 6 h the plasma level of salicylates was followed after oral administration of aspirin. The plasma levels of salicylic acid were significantly lower in bull than in heifer calves during the whole observation period. The toxicity of the drug was higher in female animals.

[Effect of tylosin in pigs]. / Ucinek tylosinu u prasat

The effect of tylosine and sulphadimidine, chlortetracycline, and bacitracin in feed was studied in 1275 piglets from 120 litters; the values obtained were compared with the control group given no antibiotics. Three Tylan injections were applied to a half of the animals on the 2nd, 5th, and 28th day after birth. The Tylan program did not lead to any significant reduction of piglet mortality before the 50th day of life. In neither of the groups did Tylan injections reduce mortality at the level of statistical significance. From the age of 56 days, the Tylan-application program provides statistically significant weight gains, as compared with other groups. The group with Czechoslovak antibiotics had the same weight as the group fed without antibiotics. The occurrence of pathological and anatomic findings on lungs showed no statistically significant differences in the two groups. The presence of tylosine in blood could not be ascertained after the oral application of even much higher doses than those used in the Tylan-application program. Small incidence of rhinitis does not allow for drawing any conclusions concerning the effects of Tylan.