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  • 1
    Electronic Resource
    Electronic Resource
    Improved penetration of aminoglycosides and fluoroquinolones into the aqueous humour of patients by means of Acuvue contact lenses (1999)
    Springer
    European journal of clinical pharmacology 55 (1999), S. 317-323 
    Details
    ISSN: 1432-1041
    Keywords: Key words Aqueous humour penetration ; Fluoroquinolones ; Aminoglycosides
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: In order to improve the penetration of topically applied drugs in ophthalmology, the suitability of hydrophilic contact lenses (Acuvue, Vistacon, power −1.0 D) as a drug delivery system for antibiotics was tested. A prospective study was undertaken to determine the transcorneal penetration of five topically applied aminoglycosides and fluoroquinolones into the aqueous humour of patients. Methods: Two hundred and sixty-five patients undergoing cataract extraction received 0.3% gentamicin, kanamycin, tobramycin, ciprofloxacin or ofloxacin solution by two different modes of administration: either as eye drops (nine drops every 15 min, starting 2 h prior to surgery) or by means of a drug delivery system (Acuvue contact lenses soaked for 1 h in eye drop solution without preservatives, 1–5 h prior to surgery). At the beginning of cataract extraction, 50–100 μl aqueous fluid was aspirated from the anterior chamber and immediately stored at −80 °C. Antibiotic concentrations were measured using fluorescence polarisation immuno-assays (aminoglycosides) or high-performance liquid chromatography (fluoroquinolones). Results: After soaking for 1 h in 0.3% eye drop solutions, Acuvue contact lenses released about 190–250 μg aminoglycoside and ofloxacin and 1000 μg ciprofloxacin. These amounts are considerably lower or in the same order of magnitude than obtained with application of eye drops (1350 μg). From the aminoglycosides tested, only gentamicin and tobramycin, but not kanamycin, were able to penetrate into the aqueous humour of patients. After the wearing of antibiotic-soaked lenses, mean aqueous humour concentrations were higher than after the use of eye drops. This difference reached significance in tobramycin (1.09 (1.30) μg · ml−1 vs 0.49 (0.79) μg · ml−1), ciprofloxacin (1.23 (0.60) μg · ml−1 vs 0.38 (0.33) μg · ml−1) and ofloxacin (5.55 (2.53) μg · ml−1 vs 0.56 (0.37) μg · ml−1). The percentage of patients with aqueous humour concentration above the MIC90 of Staphylococcus epidermidis, the most common cause of postoperative endophthalmitis, was 92% and 100% after wearing ciprofloxacin- or ofloxacin-soaked lenses, respectively. Conclusion: Gentamicin and tobramycin penetrated into the aqueous humour of patients, whereas kanamycin was not able to overcome the corneal barrier. Acuvue contact lenses soaked in 0.3% eye drop solutions can release sufficient amounts of gentamicin, ciprofloxacin and ofloxacin to produce bacteriostatic concentrations in the humor aquosus. Acuvue contact lenses can be recommended as a drug delivery system for fluoroquinolones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050635
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of mezlocillin and sulbactam under continuous veno-venous hemodialysis (CVVHD) in intensive care patients with acute renal failure (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 111-115 
    Details
    ISSN: 1432-1041
    Keywords: Key words Mezlocillin ; Sulbactam; pharmacokinetics ; hemodialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care. Methods: In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the β-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg · l−1 for mezlocillin and 5 mg · l−1 for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n=5) and/or sulbactam (n=4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver. Results: The clearances by CVVHD (CLCVVHD) for mezlocillin ranged between 11.0 and 44.9 ml · min−1 and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CLCVVHD ranged between 10.1 and 22.8 ml · min−1 and serum half lives were 4.25–6.11 h, independent of liver function. Conclusion: Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050347
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  • 3
    Electronic Resource
    Electronic Resource
    Comparison of several approaches of therapeutic drug monitoring of cyclosporin A based on individual pharmacokinetics (2000)
    Springer
    European journal of clinical pharmacology 56 (2000), S. 43-48 
    Details
    ISSN: 1432-1041
    Keywords: Key words Cyclosporin A ; Kidney transplant patients ; Individual pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The clinical outcome of patients after organ transplantation is correlated with cyclosporin A (CyA) exposure. It is generally accepted that the area under the concentration–time curve (AUC) provides a reliable means for drug exposure. However, in routine therapeutic drug monitoring (TDM) of CyA, trough levels are mostly used. Currently, a number of different new concepts of CyA-TDM, including approaches such as single, double or triple time-point and abbreviated AUC determinations, have been introduced. The purpose of this study was to compare the predictive value of the different strategies of TDM. Methods: Calculations were based on 40 individual concentration–time profiles after oral administration of CyA to patients who had been included into an ongoing prospective clinical trial. Non-compartmental analysis was used to calculate the AUC0–12h. Multiple linear regression was performed to describe the relationship between the different sets of blood concentrations and the respective AUC0–12h as well as to evaluate their predictive value regarding AUC. Predictive performance was assessed by prediction bias and prediction precision, which were estimated as the mean prediction error and root mean squared error, respectively. Results: When comparing the various combinations of time points, it was found that one-point approaches showed the strongest differences with regard to the predictive value; the associated r2 values differed from 0.203 to 0.792. The two and three time-point approaches showed lower differences – r2 0.802–0.972. The four-point and five-point approaches (r2 0.942–0.982) were the strongest predictors for CyA AUC0–12h. Relative bias ranged from −27.7% to 63.8% and changed significantly when multiple-point predictors were used. In those cases, the predictive performance improved. Considering the predictive performance as well as the smallest bias and highest prediction precision, C3, C1 + C3, C1 + C3 + C6 and C1 + C2 + C3 + C6 were the best predictors. Conclusion: The results of this study indicate that in kidney transplant patients a clinically sufficient precise estimation of the CyA AUC is possible using two or three concentration–time points.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050718
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  • 4
    Electronic Resource
    Electronic Resource
    Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humour of patients by different topical application modes (1997)
    Springer
    European journal of clinical pharmacology 53 (1997), S. 251-255 
    Details
    ISSN: 1432-1041
    Keywords: Key words Fluoroquinolones ; Topical application ; Aque-ous humor penetration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objectives: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humour. Methods: Two hundred and twenty-four patients undergoing cataract extraction received 0.3% ciprofloxacin, norfloxacin or ofloxacin eye drops by two different administration modes with different frequencies and intervals of application. At the beginning of cataract extraction (0.5–3 h after the last drop), 50–100 μl aqueous fluid was aspirated from the anterior chamber and immediately stored at −80 °C. Antibiotic concentrations were measured using high-performance liquid chromatography. Results: Generally, topical ofloxacin and ciprofloxacin yielded aqueous humour levels higher than topical norfloxacin. The highest concentrations of all tested fluoroquinolones were measured after using an application mode, in which one drop was given every 15 min between 0600 hours and 0800 hours, prior to operation. When applied by this mode, ciprofloxacin achieved a mean aqueous level of 0.380 (±0.328) μg · ml−1 (range 0.033–1.388 μg · ml−1), norfloxacin 0.182 (0.118) μg · ml−1 (range 0.038–0.480 μg · ml−1) and ofloxacin 0.564 (0.372) μg · ml−1 (range 0.064–1.455 μg · ml−1). These mean concentrations were above the minimum inhibitory concentration (MIC90), concentrations required for inhibition of 90% of pathogen strains in vitro of gram-negative bacteria, such as Proteus mirabilis and Escherichia coli. Therapeutic values above the MIC90 of Staphylococcus epidermidis, the pathogen causing eye infections most frequently, were reached by 67.5% of patients after ofloxacin and by 41% after ciprofloxacin, but never after norfloxacin treatment. Conclusion: Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humour concentration. This fluoroquinolone may be an useful ophthalmic agent for topical antibacterial management, but it does not seem to be prophylactically effective against Streptococcus pneumoniae or Pseudomonas aeruginosa.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050371
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  • 5
    Electronic Resource
    Electronic Resource
    Penetration of ceftazidime into human pancreas (1993)
    Springer
    Infection 21 (1993), S. 229-234 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Der Einsatz von Antibiotika bei schwerer akuter Pankreatitis (Stadium II und III) ist indiziert, da bakterielle Komplikationen häufigste Todesursache sind. Ceftazidim wurde hinsichtlich seiner Permeation in das Pankreassekret, in gesundes und chronisch entzündetes Pankreasgewebe sowie in nekrotische Areale bei schwerer Pankreatitis des Menschen untersucht. Im Pankreassekret fand sich 60 Minuten nach intravenöser Gabe von 35 mg/kg eine Spitzenkonzentration von 12,9±5,9 mg/l. Das sind 32% des korrespondierenden Serumspiegels. Die Gewebespiegel variierten, in Abhängigkeit vom Enzündungsstadium, zwischen 9 und 79% der jeweiligen Serumkonzentration. Auch in Pankreasnekrosen ließen sich nach fünftägiger Behandlung (3 × 2 g) Ceftazidimspiegel zwischen 1,8 und 6,9 mg/kg nachweisen. Somit sind in allen untersuchten Kompartimenten ausreichend hohe, antibakterielle Wirkspiegel nach Gabe von Ceftazidim in therapeutischer Dosierung nachweisbar, so daß sich aus pharmakokinetischer Sicht Ceftazidim als ein potentiell geeignetes Präparat bei Pankreatitis anbietet.
    Notes: Summary The use of antibiotics in patients with severe acute pancreatitis (stage II and III) is indicated since bacterial complications are the most common cause of death in these patients. In the present study the penetration of ceftazidime into pancreatic juice, into healthy and chronically inflamed pancreatic tissue as well as into necrotic regions in cases of severe acute pancreatitis was investigated. A peak concentration of 12.9±5.9 mg/l was found 60 min after intravenous administration of 35 mg/kg of the drug, which is 32% of the corresponding serum levels. Pancreatic tissue concentrations varied between 9 and 79% of the corresponding serum levels, depending on the stage of inflammation. After five days of antibiotic treatment with doses of 2 g t.i.d., concentrations between 1.8 and 6.9 mg/kg were detected even in pancreatic necroses. This suggests that sufficient antibacterial levels of ceftazidime were present in all pancreatic compartments analyzed following administration of common therapeutic dosages. Therefore, from a pharmacokinetic point of view, ceftazidime could be a potentially effective drug for the treatment of pancreatitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01728896
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    Paper (German National Licenses)
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