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Biomedical subjects

D Höffler

Publications and source records attributed to D Höffler.

At least 19 recordsLinked to original sources
PubMed1997

Biapenem pharmacokinetics in healthy volunteers and in patients with impaired renal function.

Biapenem (CAS 120410-24-4) is a new broad spectrum antibiotic agent from the group of carbapenem antibiotics. Results of a pharmacokinetic study in eight volunteers, 17 patients with variant degrees of renal impairment and in addition 13 haemodialysis patients, both on (n = 8) and off dialysis (n = 5), are reported. A single dose of 500 mg biapenem was administered i.v. over 30 min; blood and urine samples were collected up to 24 h post infusion in volunteers and up to 48 h in patients. Concentrations were determined by microbiological assay using the cup plate method. The tolerance was good. The renal function in patients was determined using single shot 51chromium-EDTA clearance. The calculation of pharmacokinetic parameters was performed non-compartmentally as well as based on an open two-compartment model. Although the compound is eliminated extrarenally in considerable amounts (approximately 46% in volunteers), an important prolonged elimination in renal dysfunction was found. This was mainly due to decreased renal elimination but also partly due to decreased extrarenal clearance. A dose reduction factor (DRF) is calculated derived from the ratio of the areas under the serum concentration curve (AUC), in normal and impaired renal function. Dosage suggestions are made. The compound is eliminated considerably by haemodialysis. It is therefore recommended that biapenem is given after haemodialysis or in double the dose on haemodialysis days.

Adult↗
PubMed1996

Pharmacokinetics of meloxicam in patients with end-stage renal failure on haemodialysis: a comparison with healthy volunteers.

OBJECTIVE: The pharmacokinetics of meloxicam have been studied following administration of a single 15-mg capsule to 12 patients with end-stage renal failure. Pharmacokinetic parameters were determined after haemodialysis. The pharmacokinetic profile obtained in these patients is compared to data obtained from age- and gender-matched healthy volunteers. RESULTS: Total plasma meloxicam concentrations were lower in patients with end-stage renal failure (AUC0-infinity 12.6 micrograms.h.ml-1) in comparison with healthy volunteers (AUC0-infinity 39.3 micrograms.h.ml-1). This was reflected by an increase in total clearance (+211%). However, there was an enhanced free meloxicam fraction (unbound drug) in the end-stage renal failure patients (0.9% vs. 0.3% in healthy volunteers). This was observed in association with raised free Cmax (5.0 vs. 2.6 ng/ml) but similar free AUC0-infinity (0.13 vs. 0.11 microgram.h.ml-1) in both groups. Therefore, the raised free fraction is compensated for by the increased total clearance such that no accumulation of meloxicam occurs. Meloxicam plasma concentrations were similar before and after haemodialysis. CONCLUSION: Meloxicam has displayed a pharmacokinetic profile in end-stage renal failure which is similar to that observed for other highly protein bound nonsteroidal anti-inflammatory drugs (NSAIDs). However, in view of the higher free Cmax value, and despite no evidence of accumulation, it may be prudent to treat this group of patients with a 7.5-mg dose of meloxicam. This is the lower dose normally recommended for adults. Meloxicam is not dialysable.

Adult↗
PubMed1995

[Antibiotic therapy in general practice].

Antibiotic therapy only makes sense if a bacterial infection exists. Strategies are discussed how viral infections--the most important reason of fever in general practise--can be differed from bacterial infections. Of special importance is e.g. CRP which only rises in case of a bacterial infection. Its decline shows that therapy is successful and that the antibiotic therapy can be discontinued. If the location of the infection is known (e.g. urinary tract), one can expect certain microorganisms and their sensitivity to antibiotics. With this kind of "calculated therapy" the use of "wrong" antibiotics can be minimized. The antibiotics which can be employed in general practise are discussed by terms of effectiveness, side effects, and price in relation to their indications and contraindications.

Anti-Bacterial Agents↗
PubMed1995

The Demers atrial catheter: experience with a single-lumen silicone catheter as short- and long-term access for hemodialysis.

The Demers catheter is a silicone atrial catheter with a dacron cuff used as short- and long-term access for hemodialysis. It was implanted in 316 patients between January 1, 1987 through May 31, 1991. Data on these implantations were retrospectively analyzed and are reported here. Follow-up and analysis was possible in 404 of 417 Demers catheter implantations. The mean age of patients in this study was 61 years. For short-term use (< 91 days) 153 catheters were implanted in 135 patients, for long-term use (> 90 days) 251 catheters in 181 patients. The median life span of all 404 catheters was 87 days. The median life span for long-term use was 150 days (2-1302) per catheter and 220 days (92-1717) per patient. Catheter malfunction (arterial blood flow < 200 ml) was encountered every 876 days in the running time of the catheter. Twenty percent (n = 80) of the catheters were explanted because of complications. These included 42 cases of catheter malfunction and 22 cases of infection.

Adolescent↗
PubMed1993

Nonrenal clearance and tubular load in renal failure.

Twelve studies on the pharmacokinetics of various antibiotics (11 beta-lactams, 1 quinolone) in renal failure were re-examined on a meta-level. It was found that besides the expected (and obvious) decrease of renal clearance in impaired renal function, the nonrenal clearance (CLNR) also decreased: in terminal renal insufficiency, CLNR was approximately only half the value found in healthy subjects. A possible explanation for this could be the uremic intoxication and the resulting disturbance of the metabolic processes. Though the absolute value decreases, nonrenal clearance in renal failure is a relevant part of the total elimination: the ratio nonrenal to total elimination doubled and was even more. Furthermore, the amount of substances eliminated per nephron was found to increase. The ratio "renal clearance/glomerular filtration rate", the tubular load, increased as well. This might have positive effects (exceptionally high concentrations of antibiotics at important sites in kidney infections) but also negative consequences (higher tubular toxicity depending on the concentration).

Anti-Bacterial Agents↗
PubMed1990

Age dependence of therapy result and risk in the treatment of arterial hypertension?

In an open multicenter study, 2,012 patients with mild to moderate essential hypertension were treated for 8 weeks with the beta1-selective blocker bisoprolol. A total of 570 general practitioners participated in this study. A total of 1,597 patients whose resting diastolic blood pressure (DBP) ranged from 95 to 115 mm Hg were considered eligible for this study. Patients received one tablet of bisoprolol (5 mg) o.d. for the first 4 weeks. In patients not responding satisfactorily to treatment, the dose could be increased to 10 mg o.d. for the following 4 weeks. A total of 1,201 patients were evaluated for efficacy and all 2,012 patients were evaluated for tolerability. After 4 weeks of therapy, mean systolic blood pressure (SBP) was lowered significantly from 170+/-15 to 151+/-14 mm Hg, and mean DBP was lowered from 104+/-5 to 92+/-7 mm Hg. A further 4-week treatment lowered the blood pressure even more: mean SBP from 151+/-14 to 144+/-13 mm Hg and mean DBP from 92+/-7 to 88+/-7 mm Hg. The total extent of both SBP and DBP reduction was equal in all age groups and showed no dependency of the initial blood pressure value. At the end of the study. the responder rate was 94.9% in patients aged under 60 years, and 90.6% in patients aged over 60 years. The age group 31-40 years showed the highest responder rate (97.5%). After 8 weeks of treatment, 69.5% of the patients were still on 5 mg of bisoprolol and 27.6% on 10 mg of bisoprolol. Of all 2,012 patients, 11.6% reported side effects such as vertigo, fatigue. gastrointestinal disturbances, and headache. The incidence of adverse drug reactions was highest in the age group 31-40 years. Bisoprolol proved in this study to be an effective and safe antihypertensive agent when given to patients with mild to moderate hypertension for 8 weeks.

Adrenergic beta-Antagonists↗
PubMed1988

Pharmacokinetics of pefloxacin in normal and impaired renal function.

Ten healthy young volunteers (mean age 28 years) and 24 patients (mean age 54 years) suffering from various degrees of chronic renal failure received an infusion of 400 mg pefloxacin (1-ethyl-6-fluoro-1, 4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid) over 30 min. The blood and urine levels of pefloxacin and of the two metabolites pefloxacin-N-oxide and norfloxacin were determined using the HPLC method. Blood levels were taken after periods of 0, 60, 120, 180, 360, 600, 720, 1440, 2880, 3360 min, and in patients suffering from renal insufficiency also after 4320 min. The urine was collected and analyzed during the periods of 0-2, 2-4, 4-10 (12) h and then in longer periods up to 72 h. In all subjects, the glomerular filtration rate (GFR, by chrome-51-EDTA) and the plasma creatinine level were determined. Effective levels against bacteria lying in pefloxacin's spectrum can be found in the plasma for about 1.5 days and in the urine for about 2.5 days. Patients suffering from chronic renal failure have pefloxacin plasma levels which beyond 24 h are higher than in healthy persons. This can be explained by both: impaired renal and extrarenal elimination. The volume of distribution of the volunteer and the patient group does not differ significantly. Therapeutic urine levels could be found in patients up to 48 h after end of infusion. Even in patients requiring regular hemodialysis, therapeutic urine levels were found up to 24 h (if urine could be produced at all). The substance therefore is a suitable remedy for urinary infections in dialysis patients as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pharmacokinetics of aspoxicillin in subjects with normal and impaired renal function.

The pharmacokinetics of aspoxicillin [2S,5R,6R)-6-[(2R)-2-[(2R)-2-amino-3-(methylcarbamoyl)propionam ido]-2- (p-hydroxyphenyl)acetamido]penicillanic acid) in 10 subjects with normal kidney function and in 20 patients suffering from impaired renal function were examined after an i.v. short-term infusion of 4 g for a period of 20 min. In contrast to available semi-synthetic penicillins, aspoxicillin shows a slightly longer half-life elimination. As the substance is mainly excreted renally, the areas under the curve (AUC) are larger in cases of impaired renal function. Mathematical correlations can be established between the AUC and the renal function parameters creatinine and glomerular filtration rate. Dosage reduction factors are then derived which allow appropriate dosages to be established for the substances under examination. Dosages for differing degrees of impaired renal function are given in tables. Since sufficiently high and long-lasting urine levels are achieved, it is reasonable to use aspoxicillin as treatment of urinary tract infections in patients suffering from end-stage renal failure.

Adult↗
PubMed1987

Pharmacokinetics of ofloxacin in healthy subjects and patients with impaired renal function.

Ten healthy volunteers and 20 patients suffering from chronic renal failure of varying severity received a single dose of ofloxacin 200mg orally. Ofloxacin concentrations were determined in blood and urine, and kidney function was assessed by measuring glomerular filtration rate (GFR) and plasma creatinine concentrations. The results show that there is a relationship between the area under the concentration-time curve for ofloxacin and both GFR and plasma creatinine concentration. On the basis of these results, a means of determining suitable dosage reduction factors in patients with renal impairment is presented. It is anticipated that appropriate reductions in the amount of ofloxacin administered to such patients will reduce the risk of central nervous system side effects.

Adult↗
PubMed1987

Pharmacokinetics and dose recommendations of carumonam in renal failure.

The pharmacokinetics of (Z)-[[[(2-aminothiazol-4-yl)[[(2S,3S)-2-(hydroxymethyl)-4-oxo-1- sulfoazetidin-3-yl]carbamoyl]methylene]amino]oxo]acetic acid, disodium salt (carumonam, Ro 17-2301) after a 2 g intravenous infusion (20 min) were evaluated in 10 healthy volunteers and 20 patients with various degrees of renal failure. The main results of the kinetic parameters in healthy volunteers (mean + SD) corrected for zero infusion time and 70 kg body weight were: t1/2 alpha, 29 +/- 12 min; t1/2 beta, 108 +/- 27 min; AUCtot, 327 +/- 40 mg h/l; Vdss, 12.2 +/- 1.5 l/70 kg; urinary recovery, 78.7 +/- 8.2%; total clearance 103 +/- 13 ml/min; renal clearance, 85 +/- 13 ml/min. Because of the large variation in the degree of renal insufficiency, calculations of the mean values for the pharmacokinetic parameters in the patient group were not generally justified with the exception of the volume of distribution (Vdss = 14.4 +/- 3.0 l/70 kg). To derive dose recommendations, a regression analysis was performed using values from both the volunteer and patient group for the total area under curve (AUCtot) and glomerular filtration rate (GFR), divided by the mean AUCtot value for the volunteers. This curve can be interpreted as giving the dose reduction factor (DRF) as a function of GFR, where by definition, DRF = 1 for healthy (and young) subjects. Using this method of equivalent areas, no (or only a slight) dose reduction is necessary for patients with GFR values above 40 ml/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗