Search PubMed⌕ Search

Biomedical subjects

A Wildfeuer

Publications and source records attributed to A Wildfeuer.

At least 19 recordsLinked to original sources
PubMed1992

Equivalence of a high-performance liquid chromatographic assay and a bioassay of azithromycin in human serum samples.

Two sensitive methods for the determination of the azalide antibiotic azithromycin in human serum were compared. High-performance liquid chromatography (HPLC) and a microbiological assay were simultaneously applied to 768 serum samples obtained in a clinical study. There was excellent agreement between the azithromycin concentrations measured by HPLC and by the bioassay. The correlation coefficient for the two methods was r2 = 0.96. The precision and the sensitivity of the methods were found to be very similar.

Azithromycin↗
PubMed1992

Leukotrienes in the cerebrospinal fluid of multiple sclerosis patients.

The concentration of the leukotrienes B4 (LTB4) and C4 (LTC4) was measured in the cerebrospinal fluid (CSF) of 38 multiple sclerosis (MS) patients and 51 with other neurological diseases. The LTB4 and LTC4 levels were significantly elevated in MS compared with the controls. The findings suggest that lipoxygenase products might play a pathogenetic role in the early, encephalitogenic phase of MS. The administration of lipoxygenase inhibitors or leukotriene antagonists might well open new perspectives for the treatment of MS.

Adult↗
PubMed1992

Suppression of experimental autoimmune encephalomyelitis by a new specific inhibitor of leukotriene biosynthesis.

The actions of the specific inhibitor of leukotriene synthesis, 3-[1-(4-chlorobenzyl)-3-t-butyl-thio-5-isopropylindol-2-yl]-2,2- dimethylpropanoic acid (L-663, 536, CAS 118414-82-7) were investigated in groups of guinea pigs that had been given both low and high doses of the encephalitogenic stimulant to induce experimental autoimmune encephalomyelitis (EAE). After daily intraperitoneal application over a period of 2 to 3 weeks the substance L-663, 536 (5 mg/kg) largely suppressed the clinical symptoms of EAE in some of the animals. The difference in the clinical symptoms between those animals that had been treated with L-663, 536 and those that had not was observed primarily in the experiment with a high encephalitogenic dose. The onset of progressive paralysis of the hind limbs that was observed in approximately 80% of the control animals only occurred in 40% of the guinea pigs that were treated with L-663, 536. No paresis at all was observed in about 25% of the treated animals. In both laboratory animals studies the CNS inflammatory infiltrates were significantly less extensive in the treated animals than in the respective control groups. The release of leukotrienes B4 and C4 by circulating neutrophil granulocytes in guinea pigs under treatment with L-663, 536 was also significantly reduced--in contrast to the untreated control animals. On the basis of the present results, it may be assumed that the L-663, 536-induced suppression of EAE in guinea pigs is attributable to the inhibition of leukotriene biosynthesis.

Animals↗
PubMed1992

Relative bio-availability of sultamicillin in healthy volunteers following administration of two tablet formulations.

The pharmacokinetics of both ampicillin and sulbactam obtained from a balanced, open two-way crossover study in 20 normal adult volunteers receiving a single 375 mg oral tablet of sultamicillin administered as two different formulations--the original product (Duocid) and a generic formulation that is commercially available in Turkey--were compared. Pharmacokinetic parameters for the two formulations and for both ampicillin and sulbactam were tested for bio-equivalence by the two one-sided Student's t-test (80-120% range; P < 0.1). Area under concentration--time curves and maximum concentrations for both components were found to be non-equivalent for the two formulations, the generic formulation having consistently lower mean values. The results were consistent with studies of the in vitro release of sultamicillin from the two tablets. It is concluded that the generic formulation is pharmacokinetically inferior to the original product.

Adult↗
PubMed1991

Pharmacokinetics of ampicillin and sulbactam in patients undergoing heart surgery.

The pharmacokinetics of ampicillin and sulbactam, a new beta-lactamase inhibitor, were investigated in 16 patients undergoing prosthetic cardiac valve insertion. The combination of 2 g of ampicillin and 1 g of sulbactam was administered as perioperative prophylaxis intravenously over 3 to 6 days. Several serum pharmacokinetic parameters were similar for the two drugs after three intravenous doses were given to patients following surgery. The half-lives of elimination of ampicillin and sulbactam were 79 +/- 4.9 and 88 +/- 5.9 min, the volumes of distribution were 15.6 +/- 1.4 and 17.7 +/- 1.2 liters/70 kg, and the total plasma clearances were 144.4 +/- 14.5 and 147.2 +/- 14.5 ml/min, respectively. The peak concentrations of ampicillin and sulbactam in serum were calculated to be 134.3 +/- 1.3 and 58.3 +/- 1.2 micrograms/ml, respectively. Ampicillin and sulbactam rapidly penetrated from the blood into various tissues collected during heart surgery, such as sternum, pericardium, myocardium, and endocardium. The concentrations of ampicillin in tissue ranged from 17.8 +/- 9.9 to 50 +/- 29.5 micrograms/g, and those of sulbactam in tissue ranged from 8.8 +/- 6.2 to 19.6 +/- 10.1 micrograms/g. The concentrations of ampicillin and sulbactam in serum and tissue also apparently exceeded the MICs against most beta-lactamase-producing bacteria usually involved in postoperative wound infections and prosthetic valve endocarditis. The ratio of the two compounds was approximately 2:1 in serum and in the various tissues affected by the operation. The pharmacokinetics of ampicillin and sulbactam in serum and investigated tissues suggest that the combination of the two beta-lactams will be effective in the perioperative prophylaxis of patients undergoing heart surgery.

Aged↗
PubMed1991

[Interactions of fluconazole and phagocytic cells].

Fluconazole is a triazole compound with a coefficient of distribution P at pH 7.4 of 1.6 (log P = 0.2), and has thus both hydrophilic and lipophilic properties. The physicochemical and pharmacokinetic profiles of fluconazole are clearly different from those of other azole antimycotics. 3H-labelled fluconazole penetrates very rapidly into granulocytes and monocytes (macrophages) isolated from volunteers. The concentrations of the triazole in the granulocytes are about 28% and in the macrophages about 63% higher than in the extracellular milieu. At the concentrations examined (5, 10 and 20 micrograms ml-1) fluconazole damages cells of Candida albicans which have been phagocytized by granulocytes or by macrophages. A clear synergy between fluconazole and the phagocytes can be demonstrated.

Candida albicans↗
PubMed1991

[Stability of beta-lactamase inhibitors and beta-lactam antibiotics in parenteral formulations as well as in body fluids and tissue homogenates. Comparison of sulbactam, clavulanic acid, ampicillin and amoxicillin].

Stability of beta-Lactamase Inhibitors and beta-Lactam Antibiotics in Parenteral Formulations as Well as in Body Fluids and Tissue Homogenates/Comparative studies with sulbactam, clavulanic acid, ampicillin and amoxicillin. The beta-lactamase inhibitors and the beta-lactam antibiotics are markedly different in chemical stability. The comparative examination of 4 different infusion solutions at 4 degrees C, 25 degrees C and 37 degrees C gives the following sequence of decreasing stability: sulbactam (CAS 68373-14-8), ampicillin (CAS 69-53-4), amoxicillin (CAS 61336-70-7) and clavulanic acid (CAS 58001-44-8). It is particularly striking that the two beta-lactamase inhibitors, sulbactam and clavulanic acid, behave very differently. Sulbactam is also much more stable than clavulanic acid to incubation at 37 degrees C in body fluids or in tissue homogenates. The differences in the stability of the individual drugs should be born in mind during clinical use of combination formulations such as sulbactam/ampicillin (Unacid) and clavulanic acid/amoxicillin.

Amoxicillin↗
PubMed1990

Suppression of experimental autoimmune encephalomyelitis by sulfasalazine.

It has recently been suggested that the sulfidopeptide leukotriene C4 (LTC4), a 5-lipoxygenase product of the arachidonic acid metabolism and one of the most potent mediators of vascular permeability, might be involved in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS). Subsequently, 20 guinea pigs with EAE were treated with sulfasalazine, a substance with a proved leukotriene inhibiting effect, which has previously been described as exerting beneficial effects in patients with inflammatory bowel disease and rheumatoid arthritis. The sulfasalazine-treated guinea pigs showed a significantly better clinical outcome, as well as a significantly lower histological inflammation score compared with 19 controls.

Animals↗
PubMed1990

Interaction of fluconazole and human phagocytic cells. Uptake of the antifungal agent and its effects on the survival of ingested fungi in phagocytes.

3H-labelled fluconazole (CAS 86386-73-4) very rapidly penetrated into polymorphonuclear leucocytes (PMNLs) and macrophages (monocytes) isolated from volunteers. The concentration of the antimycotic in the PMNLs was about 28% and in the macrophages even 63% above that in the extracellular medium. At the concentrations examined (5, 10 and 20 micrograms/ml) fluconazole damaged cells of Candida albicans which had been phagocytized by PMNLs or macrophages. There is an evident synergism between therapeutically attainable concentrations of fluconazole and phagocytic cells and this militates against the intracellular survival of the fungus.

Candida albicans↗
PubMed1990

Mechanism of azithromycin uptake in human polymorphonuclear leucocytes.

The new antibiotic azithromycin (CP-62.993) is enriched in human polymorphonuclear leucocytes by up to 300-fold the extra-cellular concentrations. To approach an understanding of the underlying mechanism of this unique behavior of azithromycin, some characteristics of the uptake process were investigated in vitro. The speed of the uptake in human polymorphonuclear leucocytes was found to be independent of the extracellular starting concentrations of azithromycin. There was no indication of saturation up to extracellular concentrations of 100 micrograms/ml. The uptake was largely determined by incubation temperatures. At 4 degrees C no penetration into the cells could be observed. The activation energy of azithromycin uptake came to 144 kJ mol-1, twice the value of erythromycin uptake. The presence of various inhibitors of cell metabolism did not change the intracellular accumulation compared to control, nor did the presence of some agents which interfere with certain transport channels. These findings suggest that passive diffusion is an essential mechanism of azithromycin transport through the phagocyte membrane, while active transport is less important. The high cellular enrichment of azithromycin and the relatively high activation energy of the uptake process could be explained by accumulation of the drug in phagocytic lysosomes and this would also be in keeping with pH partition considerations.

Adult↗
PubMed1990

In vitro activity against clinically important gram-positive and gram-negative bacteria of sulbactam, alone and in combination with ampicillin, cefotaxime, mezlocillin, and piperacillin.

The in vitro effects of the single agents, and the synergistic/antagonistic action of three different combinations of ampicillin (AMP, CAS 69-53-4), cefotaxime (CTX, CAS 63527-52-6), mezlocillin (MEZ, CAS 51481-65-3), and piperacillin (PIP, CAS 61477-96-1) with the beta-lactamase inhibitor sulbactam (SUL, CAS 68373-14-8) were determined against 675 gram-positive and gram-negative, both aerobic and anaerobic bacteria. All the combinations of sulbactam and the antibiotics (1: 1, 1:2 and 1:4) exhibited very similar synergistic action. The percentage of the total strains tested for which synergistic activity was found was 51% with SUL + AMP (1:1), 24% with SUL + CTX (1:1), 31% with SUL + MEZ (1:1), and 28% with SUL + PIP (1:1). A fourfold or greater reduction of MIC's in the comparison with the antibiotics alone was found with 23% of the total strains tested for the SUL + AMP, with 9% of the strains tested with SUL + CTX, with 11% of the strains tested with SUL + MEZ, and with 15% of the strains tested with the SUL + PIP-combination. In the presence of sulbactam, 18% of the strains tested showed a significant reduction in the number of resistant strains with ampicillin, 7% with cefotaxime, 16% with mezlocillin, 14% with piperacillin, and in parallel there was an increase in the number of fully susceptible strains (shift from resistant or moderately sensitive to sensitive) by about 14%. In comparison with the antibiotic alone, the most marked reductions in the number of resistant strains on combination with sulbactam were as follows (the percentage of reduction is shown in brackets): for SUL + AMP and Acine-tobacter spp. (39% fewer resistant strains). Citrobacter spp. (-60%), Enterobacter aerogenes (-48%), Klebsiella oxytoca (-49%), Klebsiella pneumoniae (-63%), Morganella morganii (-74%), and Proteus vulgaris (-55%); for SUL + CTX and Acinetobacter spp. (-38%), Enterobacter cloacae (-6%), Klebsiella pneumoniae (-16%), Serratia marcescens (-9%), and Bacteroides fragilis (-31%); for SUL + MEZ and Acinetobacter spp. (-68%), Citrobacter spp. (-27%), Enterobacter spp. (-23%), Klebsiella pneumoniae (-32%), and Serratia marcescens (-19%); for SUL + PIP and Acinetobacter spp. (-41%), Citrobacter spp. (-30%), Klebsiella spp. (-30%), and Serratia marcescens (-33%).

Ampicillin↗
PubMed1989

Perioperative systemic antibiotics for prophylaxis of infections in breast surgery: sulbactam/ampicillin versus mezlocillin/oxacillin.

In a prospective, randomized, open trial, efficacy of one dose of sulbactam/ampicillin (1 g:2 g) was compared to three doses of mezlocillin/oxacillin (2 g:1 g), starting with induction of anesthesia in 80 breast surgery patients with an increased risk of postoperative infection. No infections at the site of operation were seen in either group. Fever due to postoperative pulmonary complications occurred in one patient in the sulbactam/ampicillin group. The only side effect was a moderate exanthema observed in one patient in the mezlocillin/oxacillin group. In this study of the prophylaxis of patients with an increased risk of postoperative infections having the potential to jeopardize the results of surgery, a single dose of sulbactam/ampicillin was as effective as a short term course of three doses of mezlocillin/oxacillin.

Adult↗
PubMed1989

Suppression of experimental autoimmune encephalomyelitis by dual cyclo-oxygenase and 5-lipoxygenase inhibition.

The release of leukotriene C4 (LTC4), an important 5-lipoxygenase product of the arachidonic acid metabolism from polymorphonuclear leucocytes (PMNLs) of guinea pigs with experimental allergic encephalomyelitis (EAE), the animal model of MS, has been found to be significantly increased compared with healthy animals. Subsequently, the dual cyclo-oxygenase and 5-lipoxygenase inhibitor BW755C was applied to 15 guinea pigs with EAE. Two control groups (15 each) were treated with the cyclo-oxygenase inhibitor indomethacin or physiological saline, respectively. In the BW755C treated group, no animal developed symptoms of the disease in contrast to, respectively, 5 and 3 animals in the 2 other groups. Histological examination of the CNS revealed a highly significantly lower inflammation score in the BW755C treated animals, and the release of LTC4 from PMNLs was highly significantly decreased in this group compared with each of the others. The findings suggest that the vascular permeability enhancing LTC4 plays a pathogenetic role in EAE and indicate that inhibition of this sulfidopeptide leukotriene suppresses the disease. Therefore, the application of leukotriene inhibitors could contribute to the future treatment of MS.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1989

Interaction of azithromycin and human phagocytic cells. Uptake of the antibiotic and the effect on the survival of ingested bacteria in phagocytes.

14C-labeled azithromycin, a new macrolide antibiotic, was accumulated by various phagocytic cells isolated from volunteers or patients. The concentration of the antibiotic in monocytes, polymorphonuclear leucocytes (PMNLs), and alveolar macrophages was greater than that in the surrounding medium by a factor of between 200 and 668. Azithromycin penetrated somewhat more rapidly into PMNLs and monocytes than into alveolar macrophages. On the other hand the final concentration in the alveolar macrophages was greater by a factor of about 3 than that in the other two phagocytic cells. Staphylococcus aureus, Legionella pneumophila and Haemophilus influenzae previously taken up by the phagocytes were rapidly inactivated by low (0.031-0.5 micrograms/ml) concentrations of the antibiotic, which in the presence of the cells were subinhibitory. There is thus a clear synergism between azithromycin and the phagocytic cells which leads to increased intracellular killing of the bacteria.

Azithromycin↗
PubMed1989

Kinetics of the uptake of antimicrobial agents by human polymorphonuclear leucocytes.

The in-vitro rate constants of the cellular uptake and elimination of the antimicrobial agents josamycin (Wilprafen), erythromycin and tetracycline were measured in normal human polymorphonuclear leucocytes (PMNs) using the velocity gradient centrifugation technique with radiolabelled drugs at extracellular concentrations corresponding to therapeutically effective serum levels. The rate of antibiotic uptake increased stepwise in the order tetracycline less than erythromycin less than josamycin. The half-lives of the uptake came to 0.8 min for josamycin, 4.7 min for erythromycin, and 14.8 min for tetracycline. The extraordinarily rapid uptake of josamycin by PMNs corresponds to the high lipophility of the drug. The accumulation of the three tested antibiotics in PMNs occurred much faster than their elimination from the cells, suggesting directional transport of the molecules through the leucocyte membrane and/or rate limiting dissociation from intracellular binding sites. Significant differences between the drugs tested were observed in the temperature dependence of their rates of uptake. The apparent activation energies of cellular uptake amounted to 114.2 kJ mol-1 (josamycin), 68.6 kJ mol-1 (erythromycin) and 52.2 kJ mol-1 (tetracycline). There is experimental support for a contribution of the nucleoside carrier system to the membrane transport of josamycin.

Adult↗
PubMed1989

Studies on the synergism of sulbactam and beta-lactam antibiotics under in vitro conditions and in healthy volunteers after intravenous administration. Antibacterial activity in vitro, compatibility and pharmacokinetics of the drugs in combination.

Sulbactam, a new beta-lactam inhibitor, increased the in vitro activity of cefotaxime, mezlocillin and piperacillin against 803 clinical bacterial isolates. The synergism of sulbactam and these antibiotics was particular marked against 467 beta-lactamase positive strains, both aerobic and anaerobic. In the presence of sulbactam the mean minimal inhibitory concentrations (MICs) of the antibiotics against beta-lactamase positive bacteria were greatly reduced: with cefotaxime by 58%, with mezlocillin by 64% and with piperacillin by 70%. Sulbactam alone at low concentrations inhibited the growth of only a few strains (Neisseria spp., Acinetobacter spp.). The inhibitor proved to be very stable in infusion media under a variety of conditions and was compatible in vitro with 14 different beta-lactam antibiotics. The pharmacokinetics profiles of sulbactam and the antibiotics cefotaxime, mezlocillin and piperacillin were similar after infusion to healthy volunteers. The relevant pharmacokinetic parameters of the single substances were essentially unchanged when administered in combination. The general similarity between the pharmacokinetics of sulbactam and of the beta-lactam antibiotics appears to be an essential precondition for the therapeutic success of such a synergistic combination. Thus the physicochemical and pharmacological properties of sulbactam apparently permit flexible dosage in combination with different penicillins or cephalosporins and sulbactam can be administered as non-fixed combination in the clinical treatment of bacterial infections.

Adult↗