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Biomedical subjects

F Follath

Publications and source records attributed to F Follath.

At least 163 records · Page 9Linked to original sources
PubMed1986

Circadian changes in the absorption and elimination of theophylline in patients with bronchial obstruction.

Circadian variation in the serum concentration of theophylline has been reported in most patients receiving slow release oral preparations. To examine further the mechanism and clinical relevance of this change, an investigation has been made into the diurnal fluctuation in elimination kinetics during i.v. administration of theophylline and its serum concentration profile on oral treatment with a slow release preparation, in 8 hospitalized patients receiving it for bronchial obstruction. After reaching steady-state on a constant intravenous infusion, the total body clearance of theophylline (CL) was determined every 4-6 h from the steady-state concentration and the infusion rate. No systematic trend indicative of circadian changes in elimination kinetics was observed. The intraindividual fluctuation in CL during the observation period was small (coefficient of variation 4-11%). In contrast, on oral dosing a smaller area under the serum concentration-time curve was found during the night time (22.00-06.00). The results show that the circadian variation described in serum theophylline concentrations is due to delayed absorption at night. The elimination kinetics of theophylline do not change.

Absorption↗
PubMed1986

Pharmacokinetics and metabolism of quinidine in extensive and poor metabolisers of sparteine.

The pharmacokinetics and metabolism of quinidine were investigated in extensive and poor metabolisers of sparteine. No differences in plasma clearance, terminal half life, volume of distribution or cumulative urinary excretion of quinidine, 3-hydroxyquinidine and quinidine-N-oxide were observed between phenotypes. Thus, it is unlikely that quinidine metabolism is controlled by the sparteine/debrisoquine gene locus.

Adult↗
PubMed1986

Use of ciprofloxacin in the treatment of Pseudomonas aeruginosa infections.

The therapeutic efficacy and safety of ciprofloxacin was studied in 30 patients with Pseudomonas aeruginosa infections. In 20 patients ciprofloxacin was given alone and in 10 patients (including 8 compromised hosts) in combination with an aminoglycoside (9) or azlocillin (1). Ciprofloxacin was given in doses of 500 mg orally or 200-300 mg i.v. every 12 h. In patients receiving only ciprofloxacin clinical cure with eradication of bacteria was obtained in 15 patients (75%) with infections of bone and joint (6), skin and soft tissue (4), lung (2), middle ear (2) and CSF (1). Two patients with lymphoma and Pseudomonas aeruginosa pneumonia died. In patients receiving combination therapy a definite therapeutic success was achieved in four (40%). Three patients with Pseudomonas aeruginosa septicemia died. In seven patients nine bacterial strains with decreasing susceptibility of ciprofloxacin (increase in MIC from less than or equal to 0.5 micrograms/ml to 2-16 micrograms/ml) were selected (6 Pseudomonas aeruginosa, 1 Enterobacter cloacae, 1 Serratia marcescens, 1 Staphylococcus aureus). Ciprofloxacin was well tolerated. This new quinolone seems to be suitable for single drug treatment of Pseudomonas aeruginosa infections in patients with normal host defense mechanisms, while its therapeutic potential in compromised hosts requires further evaluation.

Administration, Oral↗
PubMed1986

Coronary ligation-reperfusion arrhythmia models in anesthetized rats and isolated perfused rat hearts concentration-effect relationships of lidocaine.

A comparative study of two arrhythmia models was carried out using coronary ligation and reperfusion in anesthetized rats and in isolated rat hearts. Both models allowed evaluation of the concentration-effect relationships of lidocaine as an antiarrhythmic agent. The average free plasma-water concentration that reduced the incidence of ventricular fibrillation by 50% was comparable in both models: 1.9 mg/liter in vivo and 2.1 mg/liter in vitro, respectively. In isolated rat hearts significantly higher concentrations were required for 50% reduction of ventricular tachycardia than for the suppression of ventricular fibrillation (2.9 +/- 0.13 versus 2.1 +/- 0.11 mg/liter, p less than 0.05). The good agreement between effective lidocaine concentrations in vivo and in vitro suggests that the isolated rat heart preparation is suitable for the quantitative assessment of drug effects on occlusion-reperfusion arrhythmias. A better reproducibility and easier control of drug concentrations are the advantages of the in vitro model.

Anesthesia↗
PubMed1986

Exercise-induced ventricular tachycardia as a manifestation of flecainide toxicity.

A 32-year-old woman with prolapsed mitral valve was treated with flecainide because of an episode of primary ventricular fibrillation. The drug was chosen because several hundred short runs of ventricular tachycardia unrelated to exercise were observed during 24-hour monitoring. Oral medication at a dose of 200 mg twice daily suppressed all repetitive ventricular ectopy. Eighteen months later, however, a further 24-hour recording showed a ventricular arrhythmia which was provoked early in the morning by exercise. Because the tablets were taken late in the evening and early in the morning it was suspected that toxic levels of flecainide may have produced the arrhythmia. Measurement confirmed this suspicion. Reducing the dosage abolished the arrhythmia.

Adult↗
PubMed1986

Evaluation of a rapid ultrafiltration technique for determination of quinidine protein binding and comparison with equilibrium dialysis.

The free level ultrafiltration (UF) assay by the enzyme multiplied immunoassay technique (EMIT) for determination of unbound quinidine concentration in serum (Qf) was evaluated in 50 samples obtained from cardiac patients treated with quinidine for ventricular arrhythmias. Equilibrium dialysis (ED) at 37 degrees C and high performance liquid chromatography (HPLC) served as standard methods for comparison. A good agreement was found between EMIT and HPLC at the low range of free quinidine concentration (0.1-0.7 mg/L) observed in our patients (r = 0.959). Although the correlation between UF and ED was high (r = 0.972), Qf was systematically underestimated by UF. This bias was due to the fact that UF was performed according to the recommendations of the manufacturer at 25 degrees C. No systematic differences were found when 20 additional samples were assayed by the two methods at the same temperature (25 degrees C; r = 0.992). The quinidine binding ratio showed a correlation with the serum concentration of alpha 1-acid-glycoprotein (r = 0.61). The metabolites 3(S)-hydroxyquinidine and quinidine-N-oxide did not influence the protein binding of the parent drug. The importance of adjusting the serum pH to physiological values before measurement of Qf was confirmed in this study. Our results show that, if performed under the same conditions, ED and UF yield practically identical values. Because of easy handling, the EMIT Free Level System II should be applicable under clinical conditions.

Chromatography, High Pressure Liquid↗
PubMed1986

Once a day verapamil in essential hypertension.

Pharmacodynamic and therapeutic studies with a new slow release 240 mg verapamil formulation were performed in a total of 73 patients with essential hypertension (WHO I-II, diastolic greater than or equal to 100 mm Hg). Chronic administration of slow release 240 mg verapamil, one or two tablets in the morning, resulted in 24 h plasma concentration profiles with trough levels greater than 40 ng ml-1 in 14 of 16 patients and good 24 h blood pressure control. There was no correlation between plasma verapamil or norverapamil concentration and blood pressure response. Monotherapy with slow release verapamil was well tolerated and resulted in good blood pressure control (less than or equal to 95 mm Hg diastolic) in 46 of the 57 patients. Responses were best in older patients and those with low plasma renin or higher control blood pressure. Slow release 240 mg verapamil given once daily is a simple and effective regimen.

Adult↗
PubMed1986

Pharmacokinetics of conventional and slow-release verapamil.

Verapamil is a racemic mixture of two optical isomers, the (-)-form being the more active component. Recent studies indicate a rapid hepatic transformation of (-)-verapamil, which results in different concentration-effect relationships after oral and intravenous administration. In practice the important pharmacokinetic properties of verapamil are low bioavailability (20%), predominant elimination by metabolism (greater than 95%) and a relatively short half-life (t1/2, beta is 3-5 h). After repeated dosing, the rate of hepatic drug clearance seems to decrease. Slow release (SR) formulations of verapamil may offer certain therapeutic advantages during long-term treatment. A comparison of conventional (C) and SR tablets in a 1-week treatment of eight cardiac patients showed a relative bioavailability (AUCSR/AUCC) of 90 +/- 30%. More stable serum drug levels were maintained by 12-hourly administration of SR verapamil. A further study using a new 240 mg SR preparation in patients with arterial hypertension showed that even a single daily dose can be sufficient for adequate blood pressure control over 24 h.

Adult↗
PubMed1986

Azlocillin serum levels on repetitive dosage in patients with normal and abnormal renal function.

Azlocillin serum concentrations were followed in 9 severely ill patients with various degrees of renal dysfunction after single and repetitive dosage. All patients were treated concomitantly with a cephalosporin and/or an aminoglycoside antibiotic. Elimination halflives (t1/2 beta) were highly variable (62-1, 194 min), but no significant increase occurred in patients with stable renal function during repetitive dosage due to previously described nonlinear pharmacokinetic behavior of azlocillin. However, drug accumulation was observed in patients with deterioration of renal and hepatic function. The rise in drug accumulation can be disproportionally high if both routes of elimination are affected. In such cases, careful dosage adjustment of azlocillin is required to avoid toxic side effects.

Adult↗
PubMed1985

[Pharmacology of the pulmonary circulation].

Drugs with pharmacological activity limited to the pulmonary circulation are not at present available. Serotonin antagonists, specific thromboxane A2 inhibitors and prostacyclin may offer new possibilities for the treatment of certain forms of pulmonary arterial hypertension (PAH), but their clinical efficacy remains to be evaluated. Vasodilators simultaneously influence the pulmonary and systemic vascular resistances, and their overall hemodynamic effects in patients with PAH are therefore unpredictable. Therapeutic trials with such drugs should be closely monitored to avoid serious adverse reactions. Oral administration of beta-adrenergic agents, such as salbutamol or terbutaline, is preferable to digoxin in the treatment of patients with right ventricular failure due to chronic obstructive bronchitis. Right ventricular failure following massive pulmonary embolism may be aggravated by reduced blood flow through the right coronary artery. Increase of aortic perfusion pressure (e.g. noradrenaline) should be considered as a therapeutic measure in patients with arterial hypotension.

Adrenergic beta-Agonists↗
PubMed1985

Moxalactam in nosocomial infections with Serratia marcescens.

Ten critically ill patients presenting with nosocomial infection caused by Serratia marcescens (SM) not responding to prior chemotherapy were treated in an open study with Moxalactam (MOX) alone [6] or in combination with an aminoglycoside [4]. In initial disc diffusion tests, all isolates of SM were highly susceptible to MOX. Clinically, three patients were cured and four improved. Three patients died: one from SM pneumonia, one from gangrenous cholecystitis and another from ARDS. Bacteriologically, SM were eliminated from blood cultures in all seven patients with septicemia but were recovered post mortem from the lung of one patient. In three cases with localized infection, SM were eliminated once and persisted twice. Selection of resistant SM was observed in three patients but became clinically relevant in one case only. Resistant SM strains also showed reduced susceptibility to other cephalosporins and aminoglycosides. Emergence of enterococci occurred four times, in two cases with clinical consequences. MOX is a useful drug for the treatment of SM infections, but a definite risk of selecting multiresistant SM strains and of enterococcal overgrowth must be kept in mind.

Adult↗
PubMed1985

Performance of Bayesian feedback to forecast lidocaine serum concentration: evaluation of the prediction error and the prediction interval.

The prediction performance of the Bayesian feedback method was evaluated with respect to accuracy and precision, and efficacy and safety (width of the prediction interval) on the basis of 90 predictions in 30 patients treated with lidocaine. The mean of the prediction error (PE) and the root mean squared error (RMSE) served as a measure of accuracy and precision. The variance of the standardized prediction error (SPE) was used to evaluate the estimate of the standard deviation of the prediction error. SPE was defined as PE divided by the standard deviation of the predicted concentration. The standard error of RMSE and of the variance of SPE was determined by bootstrap. The results indicate that the lidocaine serum concentration at 12 hr (C2) after starting continuous infusion can be predicted with high accuracy and precision with a single feedback measurement obtained 2-4 hr (C1) after commencement of treatment: RMSE = 20.6%. Prediction at 24 hr (C3) was less accurate: RMSE = 31.4%. Using both C1 and C2 to predict C3 improved precision (RMSE = 23.4%). The evaluation of the prediction interval revealed that the current algorithm produces an upward biased estimate, probably due to a positive bias in the estimate of the covariance matrix of the parameter estimates. It is suggested that evaluation of prediction performance should include the estimate of the prediction interval.

Bayes Theorem↗
PubMed1985

Kinetics and electrocardiographic changes after oral 3-OH-quinidine in healthy subjects.

3-OH-quinidine, a major quinidine metabolite, has been reported to have antiarrhythmic activity in animals and is suspected to contribute to the effect of quinidine in man. Four healthy subjects received 3-OH-quinidine in increasing oral doses (35, 100, 300 mg) to achieve serum concentrations in the range of those after quinidine dosing in patients. Blood and urine were collected up to 48 hours and blood pressure, heart rate, and averaged ECG complexes were recorded during 12 hours after dosing. Kinetic analysis revealed differences from published data for the parent drug. Renal clearance was 16 L/hr. The elimination t1/2 was 12.4 hours, substantially longer than that of quinidine. No systematic ECG changes were observed in two subjects with maximum concentrations of 55 and 215 micrograms/L. In the other two subjects who achieved higher maximum concentrations (447 and 918 micrograms/L), there was a significant relationship between the length of the corrected QT interval and the serum concentration of 3-OH-quinidine. These first dynamic results indicate that 3-OH-quinidine exerts effects in man resembling those of quinidine and may contribute to the antiarrhythmic activity of quinidine.

Absorption↗
PubMed1985

Review of the cardiovascular adversity of the calcium antagonist beta-blocker combination: implications for antihypertensive therapy.

The complementary antihypertensive effects of the beta-blocker/calcium antagonist combination has to be weighed against their additive and potentially detrimental negative inotropic, chronotropic, and dromotropic effects inherent in both classes of drugs. We reviewed the main adversity, particularly electrophysiological and hemodynamic effects, of combined treatments with beta-blockers and the calcium antagonists verapamil, diltiazem, and nifedipine. In patients with coronary artery disease, a different picture emerged between the verapamil and nifedipine combination with a beta-blocker. Verapamil was more often associated with conduction problems (up to 9%) and dyspnea or heart failure (up to 8%). These problems had rarely been reported with nifedipine but ankle edema (up to 11%), flushing (up to 11%), and headaches (up to 7%) predominated. The cardiovascular unwanted effects led to withdrawal in 5-8% for the verapamil/beta-blocker or nifedipine/beta-blocker combination. Although there was little cardiac adversity with the nifedipine/beta-blocker combination, the intravenous administration of verapamil in patients on beta-blockers is contraindicated and the oral verapamil/beta-blocker combination should not be sought in patients with impaired left ventricular function and when conduction disturbances are likely to occur. In treating hypertensive patients without overt coronary artery disease, there is no argument against the use of the nifedipine/beta-blocker combination but there is a need for definitive studies of the verapamil/beta-blocker combination.

Adrenergic beta-Antagonists↗