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Biomedical subjects

P Muth

Publications and source records attributed to P Muth.

15 recordsLinked to original sources
PubMed1999

[Hemophilic arthropathy as a multidisciplinary problem].

The authors have at present on their records in Slovakia 422 patients with haemophilia type A, i.e. 7.9 per 100,000 population, 76 cases of haemophilia type B, i.e. an incidence of 1.4, 189 patients with von Willebrand's disease with an incidence of 3.6 and 215 patients with hypoconvertinaemia with an incidence of 3.98 per 100,000 population. The authors present an account on the most frequent complications of haemophilia with special attention to haemorrhage into the joints and the development of serious haemophilic arthropathies. They emphasize the great contribution of team work of different medical specialists who participate in the diagnosis and treatment of these diseases.

Hemarthrosis↗
PubMed1998

Sensitive high-performance liquid chromatographic determination of arbidol, a new antiviral compound, in human plasma.

A highly sensitive and selective HPLC method was developed and validated for the determination of arbidol in human plasma. The method involves the liquid-liquid extraction of drug and internal standard from plasma with tert.-butyl methyl ether followed by evaporation and reconstitution in mobile phase. UV detection was done at 315 nm. The limit of quantification for arbidol in plasma was 0.005 microgram/ml. Linearity in plasma was proven over the whole calibration range (10.2-0.005 micrograms/ml). The method was validated according to GLP guidelines and its suitability was demonstrated by analysis of samples from a pharmacokinetic study.

Antiviral Agents↗
PubMed1996

Sensitive determination of nitrofurantoin in human plasma and urine by high-performance liquid chromatography.

A highly sensitive and selective HPLC method was developed and validated for the determination of nitrofurantoin in human plasma and urine. The method involves the liquid-liquid extraction of drug and internal standard from plasma with ethyl acetate followed by evaporation and reconstitution in mobile phase. Urine samples were simply diluted with purified water. UV detection was done at 370 nm. The limit of quantification for nitrofurantoin in plasma was 0.010 micrograms/ml. In urine nitrofurantoin could be quantified down to 0.380 microgram/ml. Linearity was proven over the whole calibration range in plasma (2.48-0.0100 microgram/ml) as well as in urine (187 micrograms/ml-0.380 microgram/ml). The method was validated according to Good Laboratory Practice guidelines and its suitability was demonstrated by analysis of samples from a pharmacokinetic study.

Anti-Infective Agents, Urinary↗
PubMed1996

Improved high-performance liquid chromatographic determination of amoxicillin in human plasma by means of column switching.

A highly sensitive and selective HPLC method was developed for the determination of amoxicillin in human plasma. After addition of buffer and internal standard, the sample was ultrafiltered and injected on to a precolumn to remove polar plasma interferences. Detection was effected with a UV detector set at 230 nm. The limit of quantification for amoxicillin was 50.1 ng/ml with an imprecision of 4.2% using 0.25 ml of plasma. Linearity was confirmed over the whole calibration range (25.4-0.0501 micrograms/ml) and the inter-day variation ranged from 2.0 to 4.5%. The method was validated according to GLP guidelines and its suitability was demonstrated by the analysis of several hundred samples in a bioequivalence study. The method can be used to determine pharmacokinetic parameters of amoxicillin in humans after a single oral dose of 500 mg.

Amoxicillin↗
PubMed1996

Improved determination of sulfadiazine in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic method for the determination of sulfadiazine in human plasma and human urine was developed and validated. The method involves the acid extraction of drug and internal standard from plasma with ethyl acetate followed by evaporation and reconstitution in mobile phase. Urine samples were simply diluted with purified water. Recovery, linearity, intra- and inter-day variation of sulfadiazine were tested and found appropriate. The quantitation range was 0.0299-15.2 micrograms/ml for plasma samples and 0.578-148.8 micrograms/ml for urine samples. The method is suitable for the quantitation of sulfadiazine from pharmacokinetic studies.

Anti-Infective Agents↗
PubMed1993

Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges.

Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae.

Aged↗
PubMed1992

Effects of 2 quinolone antibacterials, temafloxacin and enoxacin, on theophylline pharmacokinetics.

Certain quinolone and naphthyridone antibacterial agents reduce the clearance of theophylline, posing potential clinical risks for patients maintained on this bronchodilator. Whether temafloxacin also affects theophylline pharmacokinetics was assessed in a randomised double-blind 3-way crossover study in 12 healthy volunteers, using placebo and enoxacin as controls. Each volunteer participated in all 3 phases of the study, receiving theophylline plus daily divided doses of temafloxacin 800mg, enoxacin 800mg, or placebo, orally for 7 days. Aminophylline 200mg (containing 146mg theophylline) was given orally twice daily on the first 4 days. On the fifth morning, theophylline 200mg was administered intravenously, and serial blood and urine samples were collected for the following 72h. Coadministration of enoxacin significantly reduced the metabolic clearance of theophylline (approximately 65%). In contrast, during coadministration of temafloxacin, theophylline pharmacokinetics did not differ significantly from those during coadministration of placebo. No clinically significant adverse events occurred; total reported adverse events during enoxacin-theophylline administration (n = 33) were higher than those reported during temafloxacin-theophylline administration (n = 22) and theophylline alone (n = 23). Administration of temafloxacin to patients on long term theophylline therapy appears to be a safe and rational choice when treatment with a broad spectrum antibiotic is indicated.

Administration, Oral↗
PubMed1992

Effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine.

A number of quinolone antibacterial agents, particularly enoxacin, pefloxacin, pipemidic acid and ciprofloxacin, are known to decrease the clearance of methylxanthines. The effects of temafloxacin and ciprofloxacin on the pharmacokinetics of caffeine were therefore compared in a 3-way crossover study in 12 healthy young volunteers. Each volunteer received 183mg once-daily doses of caffeine in conjunction with twice-daily placebo, temafloxacin 600mg and ciprofloxacin 750mg in 3 separate phases according to a randomised sequence. A doubling of the area under the plasma concentration-time curve (77.8 vs 31.8 mg/L.h) and terminal-phase half-life (9.7 vs 4.5h) of caffeine were observed in the presence of ciprofloxacin. The magnitude of the reduction in the intrinsic clearance of caffeine produced by ciprofloxacin was greater than that described in the literature for ciprofloxacin and theophylline. This may partly be explained by intertrial differences in dosage and study design. Coadministration of temafloxacin did not have any effect on the pharmacokinetics of caffeine, confirming results of other studies suggesting that this agent does not affect methylxanthine clearance. Accordingly, it appears that restriction of caffeine intake during temafloxacin therapy is not necessary.

Adult↗
PubMed1991

Comparative pharmacokinetics of ciprofloxacin and temafloxacin in humans: a review.

Temafloxacin is a new antibacterial agent of the fluoroquinolone group. In comparison with ciprofloxacin, the current leading quinolone, temafloxacin shows higher and longer lasting plasma concentrations after equivalent doses due to an almost complete gastrointestinal absorption and a lower total clearance. Temafloxacin absorption is little influenced by food intake. Concomitant administration of antacids should be avoided; a time interval of at least 2 hours should elapse between intake of either quinolone and an antacid. Both quinolones are excreted mainly by the kidney. They differ in tubular secretion, which is high for ciprofloxacin and low for temafloxacin. The overall nonrenal elimination is similar for both compounds. Ciprofloxacin has a slightly higher extent of metabolism, while temafloxacin probably has a higher transintestinal elimination. The biliary excretion of both compounds is in the same range. The longer half-life of temafloxacin enables a once-daily dose regimen, whereas the usual recommended dosage of ciprofloxacin is twice daily. For both quinolones the apparent volumes of distribution per body weight are significantly above unity, indicating good tissue penetration with intracellular uptake. The concentrations in the extracellular fluids are directly related to the corresponding plasma concentrations. The penetration of temafloxacin into the body fluids investigated--tears, nasal secretion, saliva, sweat, prostatic and seminal fluid--in general exceeds that of ciprofloxacin (with the exception of seminal fluid). Unlike ciprofloxacin, there is no drug interaction with methylxanthines. Comparative clinical studies reflecting the complex interrelating factors of host and pathogens are needed to demonstrate the significance of the pharmacokinetic differences between temafloxacin and ciprofloxacin.

Aging↗
PubMed1990

Penetration of the active metabolite of nabumetone into synovial fluid and adherent tissue of patients undergoing knee joint surgery.

The concentration of 6-methoxy-2-naphthylacetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone under steady-state conditions. 6-MNA is the principle metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. Patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of nabumetone 1 g in the evening starting 4 days prior to surgery. On day 1 an additional loading dose of nabumetone 1 g was given in the morning. At the time of surgery (day 5), blood, synovial tissue and fibrous capsule tissue were taken simultaneously. The samples were analysed by high performance liquid chromatography. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 mg/L, in synovial fluid 34.79 mg/L, in synovial tissue 19.33 mg/g and in fibrous capsule tissue 11.43 mg/g. Under steady-state conditions mean synovial fluid levels of 6-MNA were higher than after administration of a single dose and, in common with levels in synovial tissue, persist in a range sufficient for in vitro cyclo-oxygenase inhibition.

Administration, Oral↗
PubMed1989

[Enoxacin concentrations in serum and in the wall of the colon during colorectal surgery].

For successful prophylaxis of postoperative infections in colorectal surgery the administered antibiotic must reach sufficiently high concentrations in plasma and gut wall. Therefore, in ten patients receiving 400 mg enoxacin orally about 2 h prior to operation (in addition to their routine perioperative intravenous prophylaxis with amoxicillin and clavulanic acid) concentrations of enoxacin were determined by HPLC in plasma (samples were taken at the beginning of operation, time of tissue sampling and each hour during the operation) and in gut wall. We found the following plasma concentrations (mean +/- S.D.): beginning of operation 2.53 ( +/- 1.07) mg/l, 1 h later 2.08 ( +/- 0.82) mg/l, 2 h later 1.60 ( +/- 0.65) mg/l. At the time of tissue sampling (on an average 185 min after the enoxacin dose) the plasma concentration was 2.27 ( +/- 1.02) mg/l, the gut wall concentration was 3.74 ( +/- 1.58) mg/kg, the ratio between the two concentrations was 1.70 ( +/- 0.27). It seems warranted to study orally administered enoxacin (in combination with an antibiotic against anaerobes) in prophylaxis of infections after colorectal surgery.

Aged↗
PubMed1988

Pharmacokinetics and body fluid penetration of fleroxacin in healthy volunteers.

The pharmacokinetics of fleroxacin after oral administration of 400 mg fleroxacin in twelve healthy volunteers were investigated. All drug analysis was carried out by HPLC. Pharmacokinetic analysis was done by non-compartmental methods. We found that fleroxacin achieves high plasma levels of 5.2 +/- 1.1 mg/l after 1.2 +/- 0.7 h. The high AUC-value of 60.4 +/- 8.4 mg.h/l is the result of complete absorption and the long half-life of 10.8 +/- 1.6 h. The total, renal and non-renal clearance of fleroxacin were 107.9 +/- 15.1, 67.6 +/- 11.8 and 40.3 +/- 14.5 ml/min respectively. The volume of distribution Vd beta/F was 101.4 +/- 21.9 or 1.32 +/- 0.28 l/kg. Fleroxacin penetrated well into saliva (66%), nasal secretions (223%), tears (69%) and sweat (43%). On the basis of these findings once a day administration deserves consideration in the further clinical development of fleroxacin.

Adult↗
PubMed1988

Metabolism of fleroxacin in man.

The metabolism of fleroxacin was studied in 12 healthy volunteers by use of a newly developed high pressure liquid chromatographic assay. Desmethylfleroxacin and fleroxacin N-oxide were identified as the major metabolites of fleroxacin in plasma and urine. The maximum concentrations of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide in plasma were 5.2 +/- 1.1, 0.0683 +/- 0.0151 and 0.0634 +/- 0.0090 mg/l reached at 1.2 +/- 0.7 h, 2.2 +/- 0.8 h and 6.2 +/- 2.4 h respectively (one subject excluded from analysis). The plasma AUC was between 1.0 and 2.6 mg.h/l for either metabolite and between 47.9 and 75.1 mg.h/l for the parent compound. The terminal half-life of desmethylfleroxacin was higher than that of unchanged fleroxacin and similar to the half-life of fleroxacin N-oxide. In urine unchanged fleroxacin, desmethylfleroxacin and fleroxacin N-oxide accounted for 59.9%, 6.8% and 6.3% of the dose of fleroxacin. The renal clearance of fleroxacin, desmethylfleroxacin and fleroxacin N-oxide were 67.6, 300.9 and 324.8 ml/min respectively. We conclude that demethylation and N-oxidation of fleroxacin affects the distribution and elimination characteristics significantly. Renal clearance increased, and it is suggested that the volume of distribution may increase also.

Adult↗
PubMedDate not supplied

[6-methoxy-2-naphthylacetic acid level in plasma, synovial fluid and adjacent tissue in patients with rheumatoid arthritis or gonarthroses after a 4-day therapy with nabumetone (Arthaxan)].

The concentration of 6-methoxy-2-naphthyl acetic acid (6-MNA) in plasma, synovial fluid, synovial tissue and fibrous capsule tissue was determined in an open study with 20 patients scheduled for knee joint surgery after oral treatment with nabumetone (Arthaxan) under steady state conditions. 6-MNA is the principal metabolite of the prodrug nabumetone arising from an extensive first-pass metabolism in the liver. The patients suffering from rheumatoid arthritis (n = 12) or osteoarthritis stage III or IV (n = 8) received a daily dose of 1 g nabumetone nocte starting 4 days prior to surgery. On day 1 an additional loading dose of 1 g nabumetone was given in the morning. At the time of surgery (day 5) simultaneously blood and synovial fluid was aspirated and after medial opening of the knee joint biopsies of synovial tissue and fibrous capsule tissue were taken. The samples were analysed employing HPLC. After 4 days of treatment mean 6-MNA concentration in plasma was 40.76 micrograms/ml, in synovial fluid 34.79 micrograms/ml, in synovial tissue 19.33 micrograms/g and in fibrous capsule tissue 11.43 micrograms/g. Under steady state conditions mean synovial fluid levels of 6-MNA were higher than after application of a single dose.

Adult↗