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Biomedical subjects

A Wildfeuer

Publications and source records attributed to A Wildfeuer.

At least 37 records · Page 2Linked to original sources
PubMed1994

Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese subjects.

The effect of food intake on the pharmacokinetics of orally administered fluconazole or itraconazole was investigated in a single-dose randomized two-way crossover study in Japanese subjects. 100-mg capsules of fluconazole or itraconazole were given to two parallel groups, each of 12 male and female volunteer subjects, and plasma concentrations of the antimycotics were determined by specific assays. Gastric pH and gastric emptying times were measured by coadministration of a radiotelemetric pH capsule. Intersubject variations in drug plasma concentrations were found to be much higher with itraconazole than with fluconazole. The coefficient of variation of the AUC (0-72) after food amounted to +/- 62% for itraconazole and +/- 16% for fluconazole. The consumption of a heavy breakfast significantly delayed the tmax of both drugs by approximately two hours (p < 0.05). This effect was accompanied by a significant prolongation of gastric emptying times (p < 0.0001). Food intake had essentially no effect on the absorbed amounts of fluconazole. The median relative bioavailability (postprandial vs fasting) based on AUC (0-72) was f = 0.99, with an individual range from 0.72 to 1.15. The corresponding Cmax ratio was 1.04 (range 0.91-1.17). The effect of food on the bioavailability of itraconazole was highly variable: it ranged from marked reductions (f = 0.35) to large increases (f = 3.74) of the AUC (0-72), at a median ratio of f = 1.23. The Cmax ratios postprandial vs fasting ranged between 0.27 and 5.71 (median = 1.04). It is concluded that food had an unpredictable effect on the extent of itraconazole absorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Distribution of orally administered azithromycin in various blood compartments.

The concentrations of azithromycin in whole blood, plasma, erythrocytes and polymorphonuclear leucocytes (PMNLs) were measured in 6 healthy volunteers following the last administration of a three-day regimen of 500 mg once daily. Marked enrichment of azithromycin was observed in PMNLs; the drug concentration amounted to 119 +/- 31 (SD) mg/l 6 hours after the administration. Twelve days thereafter 42 +/- 10 mg/l azithromycin was still measured in the PMNLs, although the drug was no longer demonstrable in plasma (< 0.02 mg/l). The elimination of azithromycin from the PMNLs (half-life 210 +/- 69 hours) was clearly slower than the elimination from plasma (half-life 93 +/- 70 hours). The maximal concentrations of azithromycin in plasma (0.64 +/- 0.27 mg/l) and erythrocytes (0.17 +/- 0.06 mg/l) were much lower and occurred earlier (tmax = 3 hours) than those observed in the PMNLs. The enrichment factor for azithromycin in PMNLs relative to plasma came to 177 +/- 92 at 3 hours or 1814 +/- 706 at 120 hours after the last administration. In a parallel in vitro study, the effect of accumulation of azithromycin in PMNLs on the intracellular survival of ingested staphylococci was investigated. At subinhibitory extracellular concentrations of azithromycin as low as 0.03 mg/l (MIC = 1 mg/l), a significant reduction in bacterial viability was observed, thus demonstrating antibacterial activity of the intracellularly enriched antibiotic.

Administration, Oral↗
PubMed1994

[Biopharmaceutic properties of slow-release codeine phosphate. Drug release from ion exchangers in vitro and in vivo].

The release of bound codeine (CAS 76-57-3) from a cation exchanger was examined in vitro by the flow-through method and in vivo by measuring the plasma concentrations of codeine after administration of slow-release (Codipront Retard) and standard non-retarded drops. Both sets of results show that codeine release from the ion exchanger is protracted and continuous. Relative to the standard formulation the slow-release codeine drops give a lower maximal plasma concentration (Cmax), a delayed time of maximal concentration (tmax), slower absorption (t0.5) and protracted plasma levels. The in vitro and in vivo results were in good agreement.

Adult↗
PubMed1994

[The effects of plant preparations on cellular functions in body defense].

Two preparations of Echinacea purpurea and a preparation of Eleutherococcus senticosus increased the in vitro phagocytosis of Candida albicans by granulocytes and monocytes from healthy donors by 30-45%. The chemotactic migration of granulocytes in the Boyden Chamber was increased by 45% with an Echinacea purpurea extract. The two herbal preparations had no effect in either direction on intracellular killing of bacteria or yeasts. Echinacea and Eleutherococcus preparations did not induce in vitro transformation of lymphocytes. The mistel toe preparation examined (Viscum album) did not influence the tested functions of granulocytes, monocytes or lymphocytes of healthy donors.

Adult↗
PubMed1993

Comparison of the pharmacokinetics of three-day and five-day regimens of azithromycin in plasma and urine.

In an open crossover study, the pharmacokinetics of three-day and five-day regimens of azithromycin were compared. Fourteen healthy volunteers received oral doses of azithromycin once-daily, over three days (500 mg/day) and over five days (500 mg on day 1, followed by 250 mg/day on days 2-5). Plasma and urine concentrations were determined by HPLC. Azithromycin was found to be absorbed rapidly on the first and the last days of both regimens, with mean Tmax ranging between 2.5-3 h. On day 1, peak plasma concentrations were 0.37 mg/L and 0.31 mg/L, respectively, with three- and five-day regimens, and increased to 0.42 mg/L on the last day of the three-day regimen, but decreased to 0.18 mg/L at the end of the five-day regimen. Similarly, the AUC0-24 increased from 1.30 to 1.88 h.mg/L during the three-day regimen, and decreased from 1.24 to 0.80 h.mg/L on the five-day regimen. After absorption, azithromycin was distributed rapidly; the respective half-lives were 2.4 h and 2.2 h with the three-day and five-day regimens. Thereafter, a polyphasic decline of plasma concentrations was observed; the average half-lives between 8-48 h after administration were 27.9 h (three-day regimen) and 35.8 h (five-day regimen). In urine, 5.5% (three-day regimen) and 4.6% (five-day regimen) of the total dose was found as unchanged azithromycin over a 12-day period. The observed pharmacokinetics of azithromycin with both regimens conformed with the known pharmacokinetic behaviour of the drug. The treatment-related differences seen in the plasma concentrations were as expected from the different dosage schedules.

Administration, Oral↗
PubMed1993

Identification of Legionella pneumophila in various specimens by the polymerase chain reaction.

Amplification of the mip sequence with polymerase chain reaction (PCR) proved to be specific for Legionella pneumophila. With nested PCR, the sensitivity of the test was markedly increased. The lower limit of detection for nested PCR in the aqueous medium for live and heat-inactivated dead L. pneumophilia was approximately 1-10 bacteria/ml. The sensitivity of the method, however, was reduced by a factor of 10 to 100 when the bacteria were added to homogenised pulmonary tissue. Fixing the bacteria in aqueous suspension or in tissue homogenate with buffered 4% formalin (pH 7.3) reduced the sensitivity of the PCR by a factor of about 100. After intravenous injection of heat-inactivated bacteria in mice L. pneumophila was detected in deep-frozen samples of plasma and various tissues. The molecular biological technique of nested PCR is proposed as an additional method for the diagnosis of legionella.

Base Sequence↗
PubMed1993

Uptake and subcellular distribution of azithromycin in human phagocytic cells. Demonstration of the antibiotic in neutrophil polymorphonuclear leucocytes and monocytes by autoradiography and electron microscopy.

Azithromycin (CAS 83905-01-5), a new azalide antibiotic, reached high concentrations in alveolar macrophages obtained from patients. Uptake of [14C] azithromycin by macrophages resulted in an intracellular/extracellular concentration ratio of approximately 634 after 90 min incubation. Electron microscopic autoradiography provided visual evidence for the marked uptake and localization of [3H] azithromycin in human neutrophils and monocytes isolated from healthy volunteers. Quantitative analysis of the autoradiographs showed the distribution of azithromycin over the various compartments of the phagocytic cells.

Autoradiography↗
PubMed1993

Pharmacokinetics and tolerance of fluconazole suppositories in healthy volunteers.

Fluconazole (Diflucan, CAS 86386-73-4) suppositories offer a novel way to administer this systemically active antimycotic. The pharmacokinetics and toleration of this new formulation have now been examined in healthy adult volunteers. In crossover experiments the bioequivalence was demonstrated for 200 mg suppositories and 200 mg capsules, and for 25 mg suppositories and 25 mg fluconazole in an oral suspension. The mean bioavailability of the 200 mg suppository relative to the capsule was about 93%. The mean bioavailability of the 25 mg suppository relative to the oral suspension was 107%. Absorption of fluconazole after administration of the suppositories was, however, somewhat slower than after oral ingestion of the capsule or suspension. The pharmacokinetic parameters of the 200 mg and 25 mg suppositories suggest that the kinetics of rectally administered fluconazole are linear with dosage. Daily administration of the 200 mg suppository gives a continuous increase in the mean fluconazole plasma concentration, until steady-state is reached on about the 5th day. The systemic and local toleration of the fluconazole suppositories was good.

Adult↗
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↗