[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.

A set of simple aids to drug dosage adjustment in renal insufficiency.

A set of graphical aids to drug dosage adjustment is presented, consisting of 1) a nomogram for evaluation of the dosage adjustment factor, 2) a nomogram for estimation of the creatinine clearance from the serum creatinine level, 3) decision tables for selection of a clinically acceptable adjustment of the dosing regimen. The set is accompanied by a list of percentage fractions excreted unchanged in urine for selected drugs and requiring adjustment of the dosing regimen in renal insufficiency. An example of the utilization of the set is demonstrated in comparison with the usual procedures of dosing regimen adjustment.

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.

[Why is peroperative antibiotic prophylaxis of infectious complications most effective?]. / Proc je peroperacní antibiotická profylaxe infekcních komplikací nejúcinnejsí?

The concentrations of oxacillin, azlocillin, temocillin, amoxycillin, cefoperazone, cefazoline, netilmicin, clindamicin, ofloxacine in serum and coagulum take a parallel course but their content in the coagulum is ten times lower than in serum--with the exception of doxycycline which reached a 40% value of the serum level in the coagulum. From this ensues that most effective are those antibiotics which can be administered in large doses and which have a long half-life. Unfavourable are antibiotics with a narrow therapeutic range and those with a short half-life. Preoperative application of such doses which create sufficiently high and prolonged levels is the optimal method of antibiotic prophylaxis of infectious complications during surgical operations.

[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)

Cefoperazone pharmacokinetics in patients with liver cirrhosis: a predictive value of the ujoviridin test.

Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers and in 11 patients with liver cirrhosis. In the same persons, we also examined the clearance of ujoviridin--a preparation of indocyanine green. Within 12 h, 31.8 (+/- 7.6)% of the 2 g dose of cefoperazone was eliminated in the urine of healthy persons and 74.3 (+/- 7.9)% (mean +/- SD) was eliminated in the urine of cirrhotics. The biological half-life (beta-phase) of cefoperazone in healthy volunteers and in cirrhotics was 1.77 (+/- 0.25) and 4.29 (+/- 1.16) h, total clearance 1.009 (+/- 0.187) and 0.583 (+/- 0.169) ml/s and hepatic clearance 0.694 (+/- 0.174) and 0.152 (+/- 0.079) ml/s, respectively. The differences are statistically significant (p less than 0.001). We also found good correlation between total clearance of cefoperazone and clearance of ujoviridin (r = 0.842) and even better between hepatic clearance of cefoperazone and ujoviridin clearance (r = 0.957), both statistically significant. The findings suggest that the dosage of cefoperazone should be reduced in patients with liver cirrhosis and that the ujoviridin clearance test is a good indicator of impaired cefoperazone elimination.

Pharmacokinetics of cefoperazone in healthy volunteers.

Pharmacokinetics of cefoperazone was studied in 10 healthy volunteers following 15 min intravenous infusion of 2 g. Cefoperazone levels in the blood serum and in the urine were determined microbiologically. At the end of the infusion, mean serum concentrations of the antibiotic were 340.4 (+/- 81.5) mg/l, at the 4th hour after the infusion 38.4 (+/- 10.3) mg/l, and 12 hours after the infusion all subjects had detectable concentrations with the mean value 2.2 (+/- 0.7) mg/l. Within 12 hours, 33.3 (+/- 6.1) % of the total dose of cefoperazone had been eliminated in the urine. The fitting of the individual serum concentration curves and the determination of pharmacokinetic constants were done according to a two-compartment model with the aid of nonlinear least-squares regression analysis on a programmable calculator TI 59. The mean value of the biological half-life (beta phase) of cefoperazone was 1.77 (+/- 0.25) h, mean serum clearance was 61.7 (+/- 12.1) ml/min and the mean distribution volume (Vd area) was 9.44 (+/- 2.2) 1. Our data are in agreement with those previously reported in the literature. The only exception is the distribution volume, which we found to be smaller.

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.