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Biomedical subjects

H Lode

Publications and source records attributed to H Lode.

At least 271 records · Page 15Linked to original sources
PubMed1982

Supplementary dose after hemodialysis.

It is the aim of this paper to review in tabulated form the supplementary dose of drugs required after hemodialysis and to discuss the basic pharmacokinetics of these drugs in the presence of reduced renal function. This review is intended to point out practical aspects of clinical nephrology, It refers to data available from the literature. The descriptions of pharmacokinetics focus on the amount of drug in the body. The fraction of this amount removed by dialysis is replaced by the supplementary dose to maintain effective drug action. The rebound phenomenon affecting plasma drug levels after dialysis renders the calculation of the supplementary dose difficult. Linear extrapolation from plasma drug concentrations measured 6-12 h or more after dialysis may offer a solution to this problem.

Drug Administration Schedule↗
PubMed1982

Kinetic in vitro studies of antibacterial effects of the combination of new penicillins and cefalosporins against Proteus vulgaris.

In vitro studies simulating human as well as animal pharmacokinetics were performed in order to assess the combination effect of mezlocillin plus cefotaxime or cefoperazone. Different Proteus vulgaris strains exhibiting varying degrees of in vivo response to the antibiotics were selected for this study. Retardation of bactericidal efficacy was caused by the combination of mezlocillin plus cefoperazone in those strains exhibiting high degrees of beta-lactamase inducibility and being exposed to high levels of cefoperazone; lower drug levels caused indifferent effects. In any case, cultures were completely sterilized during the study period. Among the three beta-lactams studied, cefoperazone was the best beta-lactase inducer, while cefotaxime and mezlocillin exhibited only minor inducer activity. The combination of mezlocillin with cefotaxime, being only minimally active as beta-lactamase inducers, caused either indifferent or synergistic effects when simulating drug disposition in humans or animals. beta-Lactamase-negative strains exhibited only indifferent effects. The augmented bioavailability of mezlocillin due to its simultaneous administration with a cefalosporin resulted in an increased antibacterial efficacy.

Cephalosporins↗
PubMed1982

Pharmacokinetics and antibacterial efficacy in vivo of beta-lactam combinations against Proteus vulgaris.

The pharmacokinetics and antibacterial efficacy of mezlocillin, cefotaxime, cefoperazone and the mezlocillin/cefalosporin combinations, respectively, were studied by adopting the granuloma pouch model in rats. Exudate concentrations of mezlocillin were higher after combined i.v. injection with a cefalosporin as determined microbiologically and by high performance liquid chromatography (HPLC). Cefoperazone levels, however, were not affected. Not metabolized cefotaxime concentrations as determined by HPLC were also not increased following simultaneous injection with mezlocillin. Cefotaxime metabolite concentrations, however, were generally higher than unchanged cefotaxime and increased upon repeated administration of cefotaxime alone and to a greater extent when combined with mezlocillin. Antibacterial efficacy of mono- or combined chemotherapy was correlated to beta-lactamase inducibility of the test strains insofar as drugs acting as good or moderate enzyme inducers were ineffective in vivo. The combined therapy of mezlocillin with cefotaxime was effective in this case. This result was also correlated to the bioavailability of the beta-lactams in infected pouches. Due to the degree of beta-lactamase inducibility and production, drug levels were either decreased or not detectable.

Animals↗
PubMed1981

[Cefoperazone--a new cephalosporin antibiotic with broader spectrum of activity].

Concentration of Cefoperazone in serum and urine was determined after 1g (bolus injection) and 2g drip-infusion over a 30-minute-period in 10 healthy volunteers. The pharmacokinetic analysis was performed using an open 3-compartment model. Renal clearance was determined in three volunteers and indicates an expansive extrarenal elimination rate. 31 patients mainly with severe bronchopulmonary infections were treated with 2.0--6.0 g/day of Cefoperazone. The therapeutic results were favourable, the toleration of the drug was good.

Adult↗
PubMed1980

Significance of pleural and sputum concentrations for antibiotic therapy of bronchopulmonary infections.

Tests were done with various antibiotics (ampicillin, carbenicillin, cefazolin, cefotaxime, cephradine, ticarcillin) in order to determine the significance of sputum and pleural concentrations for adequate therapy of bronchopulmonary infections. In a total of 19 chronic bronchitis patients, it was found that the attainable sputum concentrations were rather low and that individual fluctuations were great. No clear connection was evident between dosage and concentration of antibiotics in the sputum. In 17 patients with exudative pleurisy, test data yielded in pleural kinetics largely corresponded with data from animal experiment models. The pleural cavity can be described as a partial extracellular, extravascular compartment in which the concentration course probably correlates more to the interstitial lung concentrations than to that of the sputum.

Anti-Bacterial Agents↗
PubMed1980

Clinical pharmacology of a new ureidopenicillin: Bay K 49999.

A new semisynthetic ureidopenicillin (Bay K 4999) demonstrates favorably in vitro antibacterial efficacy against human-pathogenic gram-negative rods in comparison to mezlocillin and azlocillin. A comparative paramcokinetic study was done with 10 test subjects after 30 min intravenous infusion of 4.0 g of Bay K and mezlocillin, respectively. The serum concentration course during a period of 10 h showed an open three-compartment model for both antibiotics. The urine recovery of Bay K 4999 during 24 h was only 32.6 +/- 4.3% of the applied dose. In three test subjects with normal renal function, the average renal clearance of Bay K was 61.0, the total serum clearance was 409.2 ml/min/1.73 m2. 31 patients were treated with a daily dose of 3 x 1.0--2.0 g Bay K for severe bronchopulmonary, UTI and cholangiogenic infections. The therapeutic results were good; the relatively high number of side effects should be further investigated in animal studies and require more clinical experience.

Adult↗
PubMed1980

Comparative pharmacokinetics of cefoperazone and cefotaxime.

The pharmacokinetics of cefoperazone and cefotaxime were compared in a crossover, randomized study in ten healthy volunteers (5 males, 5 females). Each subject received 2.0 gm of the study drug administered by an IV infusion over 30 minutes. Serum concentrations of cefoperazone and cefotaxime at the end of the infusion (zero time) were 254 mg/liter and 144 mg/liter, respectively. Comparative results at other times were the following: four hours, 20 mg/liter and 3 mg/liter; eight hours, 4.4 mg/liter and 0.3 mg/liter; and 12 hours, 1.2 mg/liter and 0.0 mg/liter. Twenty-one percent of the 2.0-gm single dose of cefoperazone was recovered in the urine during the first 24 hours following dosing, compared to 52% for cefotaxime. The renal clearance of cefoperazone was also determined in three patients during four hours. The results of the investigations will be discussed in view of the clinical relevance.

Adult↗
PubMed1980

[Doxycycline pellets: a suitable formulation with guaranteed bioequivalence].

Basing on the physico-chemical properties of doxycycline relevant to an optimisation of the administration of this drug a new formulation (pellets) was developed. The bioavailability and tolerability of this formulation were studied in normal subjects in a cross-over design. The drug liberation profile of the new product excludes the risk of oesophageal irritation. The gastric tolerance of the pellet formulation is significantly better than that of the comparative product. No statistically significant differences were observed in the plasma AUC, indicating bioequivalence of the dosage forms. The values for plasma peak levels did not differ significantly, and were in agreement with the results of other studies on doxycycline bioavailability. Using the experimental data, a pharmacokinetic computer simulation of the doxycycline plasma levels for multiple-dose treatment was carried out: During the usual therapeutic dosage regimen the plasma levels are maintained above the MIC value.

Adult↗
PubMed1980

[Comparative pharmacokinetics of oral cephalosporins: cephalexin, cefaclor and cefadroxil (author's transl)].

In a randomized crossover study, the pharmacokinetics of two new cephalosporin antibiotics, cefaclor (CCL), and cefadroxil (CDX), were determined after oral administration of 1000 mg (capsules) on an empty stomach in 12 normal subjects in comparison to cephalexin (CEX). Serum concentrations were measured during a period of 8 h and urine recovery during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximum serum concentrations (ymax) were 38.8 +/- 8.1 mg/l (CEX), 34.6 +/0 7.8 mg/l (CCL), 33.0 +/- 5.4 mg/l (CDX); the areas under the curve were 93.0 +/- 14.8 h . mg/l (CEX), 74.5 +/- 9.9 h . mg/l (CCL), and 108.5 +/- 18.4 h . mg/l (CDX). In a further crossover study with 6 subjects, 1000 mg CEX and CDX were given during a standard breakfast. The ymax of CEX decreased to 23.1 +/- 6.6 mg/l in contrast to CDX with an unchanged ymax of 32.7 +/- 3.4 mg/l.

Adult↗
PubMed1979

Elimination of ampicillin and gentamicin by hemofiltration.

Elimination of ampicillin and gentamicin by hemofiltration was measured in 5 and 4 patients, respectively, being treated for end stage renal failure. Serum half-life time of ampicillin after a single I.V. dose of 2 g, was found to be 2.97 +/- 0.73 h, and the filtrate concentrations declined parallel to the serum ampicillin levels, as was to be expected. The serum half-life time after a single I.V. dose of 1 mg/kg body weight gentamicin was 3.26 +/- 0.42 h, and considerably shorter than T/2 of gentamicin in conventional hemodialysis, while the filtrate concentrations increased paradoxically with declining serum levels. This could be explained by binding of this aminoglycoside to the polyacrylnitril membrane of the RP 6 dialyser used for hemofiltration.

Ampicillin↗
PubMed1979

[Pharmacokinetics of cefaclor and initial therapeutical experience (author's transl)].

Twelve normal volunteers in the fasting state were given 1000 mg cefaclor, and the serum and urine concentrations over 8 h and 24 h respectively were measured. The average peak serum concentration was 34.6 +/- 7.8 mg/l, this value being reached after 65.2 +/- 11.1 min; the half-life was 42.5 +/- 8.3 min. In another six volunteers the absorption of 500 mg of 'cefaclor following administration in the fasting state and after a test breakfast was studied. The peak serum concentrations after administration in the fasting state were 16.1 +/- 3.2 mg/l, and after a meal 12.5 +/- 1.9 mg/l; the areas under the curve did not differ. The low recovery rate of cefaclor in urine observed in this series of investigations could be partly explained by the inactivation of the substance in urine. Cefaclor was administered therapeutically to 23 patients, most of whom were suffering from bronchopulmonary infections and chronic pyelonephritis. The results of therapy were good in four patients, satisfactory in 13 patients and unsatisfactory in three patients. Intolerance was rare.

Cefaclor↗
PubMed1979

Comparative pharmacokinetics of cephalexin, cefaclor, cefadroxil, and CGP 9000.

In a randomized crossover study, the pharmacokinetics of three new cephalosporin antibiotics, cefaclor, cefadroxil, and CGP 9000, in comparison to cephalexin, were determined after oral administration, by capsules, of 1,000 mg on an empty stomach in 12 normal subjects. Serum concentrations were measured during a period of 8 h, and urine recovery was measured during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximal serum concentrations (y(max)) for cephalexin, cefaclor, cefadroxil, and CGP 9000 (in milligrams per liter) were: 38.8 +/- 8.1; 34.6 +/- 7.8; 33.0 +/- 5.4; and 23.3 +/- 7.3, respectively. The areas under the curve (in hours x milligrams per liter) were: 93.0 +/- 14.8; 74.5 +/- 9.9; 70.1 +/- 9.0; and 108.5 +/- 18.4, respectively. In a further crossover study with six subjects, 1,000 mg of cephalexin and of cefadroxil were given during a standard breakfast. The y(max) of cephalexin decreased to 23.1 +/- 6.6 mg/liter, in contrast to cefadroxil, with an unchanged y(max) of 32.7 +/- 3.4 mg/liter.

Administration, Oral↗
PubMed1979

Efficacy of reproterol assessed by the acetylcholine provocation test.

The acute broncholytic efficacy and the protective anticonstrictive effectiveness of a new beta 2-receptor stimulator, Reproterol, was tested in 16 patients with the acetylcholine (ACH) provocation test. Plethysmographic airway resistance determinations (Raw) and flow volume curves (VEmax50%/FVC) were used as assessment parameters. All patients proved susceptible to ACH provocation, in as much they demonstrated a significant rise in the Raw from 2.46 to 11.53 cm H2O/1/sec and a significant decline of the VEmax50%/FVC from 884 to 565 (ml/sec/1) following ACH administration. With Reproterol inhalation (2 puffs at 500 mu each), almost complete elimination of ACH-induced bronchial constriction was achieved. The ACH provocation with the same patients the following day, however, was almost absent 60 min after oral ingestion of 20 mg of Reproterol tablets. Dose-efficacy studies in 7 volunteers from the same group revealed a subjectively better tolerance of the 10-mg tablets, but with a correspondingly lower antibronchia constrictive efficacy.

Acetylcholine↗