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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetic characteristics of piperacillin/tazobactam (1994)
    Springer
    Intensive care medicine 20 (1994), S. S14 
    Details
    ISSN: 1432-1238
    Keywords: Piperacillin ; Beta-lactamases ; Pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Piperacillin/tazobactam is a new combination of a broad-spectrum penicillin and a beta-lactamase inhibitor. In studies in healthy volunteers, the pharmacokinetics of piperacillin combined with tazobactam were similar to those of piperacillin alone. In contrast, tazobactam administered with piperacillin achieved higher plasma concentrations and had a longer half-life than tazobactam administered alone. Intravenous infusion of 4.0 g piperacillin with 0.5 g tazobactam over 5 min resulted in mean maximum plasma concentrations of 380 μg piperacillin/ml and 35.3 μg tazobactam/ml; half-lives were 1.14 h for piperacillin and 0.92 h for tazobactam. Within 30 min of infusion, piperacillin/tazobactam achieves 16–85% of plasma concentrations in skin, muscle, lung, gallbladder, and intestinal mucosa. Plasma and tissue levels remain above the MIC90s of major pathogens for 2 h post administration. These findings show that piperacillin/tazobactam is a truly synergistic combination which can be expected to be effective in treating a wide variety of infections in the clinical setting.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01745246
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of tocainide in patients with severe renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 665-670 
    Details
    ISSN: 1432-1041
    Keywords: tocainide ; renal failure ; pharmacokinetics ; oral dosing ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The plasma levels of tocainide have been followed after oral administration of 600 mg p.o. to 20 patients with renal failure due to various causes, and to 8 healthy controls. The peak plasma concentrations in the patients with pyelonephritis (3.80 µg/ml) and interstitial nephritis (3.74 µg/ml) but not in those with glomerulonephritis (3.17 µg/ml) differed from that in healthy volunteers (3.24 µg/ml). The renal clearance of tocainide was well correlated with the endogenous creatinine clearance and was dependent on urine pH. No difference in renal clearance was observed between the patients groups. It is suggested that the changes in plasma levels are a consequence of decreased renal clearance. Creatinine clearance was shown to be a poor estimator of tocainide clearance, which suggests that extrarenal clearance plays an important role in the handling of the drug in the body. The findings are used to suggest a safe dosage regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00607912
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  • 3
    Electronic Resource
    Electronic Resource
    Steady state bioavailability of a new oral formulation of Hydergine® in geriatric patients (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 133-135 
    Details
    ISSN: 1432-1041
    Keywords: co-dergocrine mesylate ; geriatric patients ; hydergine ; bioavailability ; steady state
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The relative bioavailability of the newly developed formulation of co-dergocrine mesylate (Hydergine spezial, 1×4 mg) was determined in elderly patients under steady state conditions, with conventional Hydergine forte tablets (2×2 mg) as a reference. Both formulations were given once a day for 8 days in a randomised cross-over design. The areas under the curve showed that the bioavailability of the new tablet was about 30% higher (28±6.3%) than that of Hydergine forte. The peak plasma concentration was reached 3±0.9 h after administration. Because of its greater relative bioavailability higher plasma levels were found 2–24 hours after the Hydergine spezial formulation than after Hydergine forte tablets.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546722
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  • 4
    Electronic Resource
    Electronic Resource
    Does alpha1-acid glycoprotein reduce the unbound metabolic clearance of disopyramide in patients with renal impairment? (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 313-317 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; alpha1-acid glycoprotein ; renal dysfunction ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of disopyramide was studied in 15 patients with renal dysfunction (4 with pyelonephritis, 7 with glomerular nephritis and 4 with interstitial nephritis). The elimination rate constant of unbound disopyramide was 0.094 h−1 and CLu/f (unbound clearance divided by bioavailability) was 245 ml/min. Both the unbound renal clearance (CLR) and CLu/f were highly correlated with the creatinine clearance (CLCR). The apparent unbound metabolic clearance in the patients was approximately two-fold lower than that previously reported in normal subjects. The estimated unbound metabolic clearance in the renal dysfunction patients showed a significant negative correlation with the α1-acid glycoprotein (AAG) concentration and only a weak, non-significant correlation with CLCR. As AAG in the renal dysfunction subjects was increased in comparison with normal values, it is possible that AAG is a factor in the decrease in the apparent unbound metabolic clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558271
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  • 5
    Electronic Resource
    Electronic Resource
    Bioavailability of disopyramide in normal volunteers using unbound concentration (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 625-629 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; bioavailability ; saturable binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of disopyramide were determined in 10 healthy volunteers after a 300 mg oral dose and again after a 2mg/kg i.v. dose. The unbound clearance was 599 ml/min and the unbound renal clearance 310 ml/min. The terminal elimination rate constant of unbound drug was 0.180 h−1 after the i.v. dose and 0.203 h−1 after the oral dose. The absorption rate constant was 0.53−1 and the maximum peak concentration occurred after 3.2 h. The bioavailability was 0.809 using the area under the unbound plasma concentration time curve. Although a saturable plasma protein binding was found in all subjects the bioavailability using the total concentration, in contrast to theoretical expectations, showed the same value (0.813) as the unbound concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02456000
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  • 6
    Electronic Resource
    Electronic Resource
    Enoxacin — Pharmakokinetik und Gewebepenetration im Vergleich (1989)
    Springer
    Infection 17 (1989), S. S14 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The choice of an antimicrobial agent is primarily dependent on its antimicrobial activity and the pharmacokinetics in the host. The gyrase inhibitors differ in their antimicrobial spectrum as well as in their pharmacokinetics. In this review we compare key pharmacokinetic parameters of the most important 4-quinolones. Clearly, there are differences in their absorption, their sensitivity of the absorption process to food or di-or trivalent cations. On a weight basis enoxacin tends to have higher plasma levels then e.g. ciprofloxacin or norfloxacin and also tissue penetration of enoxacin as determined in theBody Fluid Model is superior to ciprofloxacin or norfloxacin. The elimination of enoxacin is mostly by the kidney (∼50–60% of dose) another 12–15% are metabolized in the liver. Renal failure therefore requires dose adjustments. The inhibitory effect of enoxacin on other compounds' metabolism has to be considered.
    Notes: Zusammenfassung Die Bedeutung pharmakokinetischer Parameter von antimikrobiellen Substanzen für ihren Einsatz in Klinik und Praxis gilt heute als unumstritten. Pharmakokinetische Untersuchungen sind vielfach von gleicher Bedeutung wie die Bestimmung der antimikrobiellen Aktivität, etwa der minimalen Hemmkonzentration. Die Gyrasehemmer (Chinolone) sind hierfür ein gutes Beispiel. In dem vorliegenden Beitrag werden die pharmakokinetischen Eigenschaften sowie die Gewebepenetration von Enoxacin im Vergleich zu anderen wichtigen Gyrasehemmern dargestellt. Die Resorption von Enoxacin ist auch bei gleichzeitiger Nahrungsaufnahme gut. Die für alle Gyrasehemmer beschriebene Resorptionsbeeinflussung bei gleichzeitiger Antazidagabe ist zu beachten. Bei Verabreichung identischer Mengen Enoxacin, Ciprofloxacin oder Norfloxacin erreicht Enoxacin die höheren Plasmaspiegel. Damit gehen auch höhere Gewebespiegel einher, sowohl was die absolute Konzentration anbetrifft als auch die relative Konzentration von Enoxacin im Gewebe im Vergleich zu Plasma. Die Ausscheidung von Enoxacin erfolgt überwiegend über die Niere, etwa 12–15% der Dosis werden in der Leber verstoffwechselt. Da Enoxacin den Abbau anderer Medikamente hemmen kann, muß auf mögliche Interaktionen Rücksicht genommen werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01643628
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  • 7
    Electronic Resource
    Electronic Resource
    Enoxacin-Konzentrationen im Lungengewebe (1989)
    Springer
    Infection 17 (1989), S. S21 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary For successful treatment of bacterial lung infections the administered antibiotic must reach sufficiently high concentrations in lung tissue. Therefore, the concentrations of enoxacin in this tissue were measured in ten patients requiring pulmonary surgery. In order to prevent postoperative infection, the patients received 400 mg enoxacin b.i.d. for three days. Eight h after the final dose samples of venous blood were drawn and a sample of lung tissue was removed. Using a microbiological assay, we found the following concentrations (mean ± S.D.): serum 2.36 (±0.65) mg/l, lung 6.48 (±1.54) mg/kg. With the HPLC-technique the corresponding values method were 2.37 (±0,80) mg/l and 7.41 (±3.01) mg/kg. Thus concentrations of enoxacin in lung tissue are about three times higher than the corresponding serum concentrations.
    Notes: Zusammenfassung Zur erfolgreichen Therapie einer bakteriellen Lungeninfektion muß das verwendete Antibiotikum genügend hohe Konzentrationen im Lungengewebe erreichen. Bei zehn Patienten, die an der Lunge operiert wurden, wurden die Enoxacin-Konzentrationen in diesem Gewebe bestimmt. Zur Prophylaxe einer postoperativen Infektion erhielten die Patienten drei Tage lang 2×400 mg Enoxacin pro Tag. Acht Stunden nach der letzten Gabe wurden venöse Blutproben und Lungenproben gewonnen. Mit einer mikrobiologischen Bestimmungsmethode fanden sich folgende Konzentrationen (Mittelwert ± Standardabweichung): Serum 2,36 (±0,65) mg/l, Lunge 6,48 (±1,54) mg/kg. Bei Anwendung der HPLC-Technik waren die entsprechenden Werte 2,37 (±0,80) mg/l und 7,41 (±3,01) mg/kg. Die Lungenkonzentrationen von Enoxacin sind ca. dreimal höher als die entsprechenden Serumkonzentrationen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01643630
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  • 8
    Electronic Resource
    Electronic Resource
    Bronchopulmonale Penetration von Enoxacin (1989)
    Springer
    Infection 17 (1989), S. S23 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary We analysed enoxacin concentrations in plasma, saliva, bronchial secretions, bronchoalveolar lavage fluid, and alveolar macrophages in nine patients five hours after the last dose (400 mg enoxacin b.i.d. per os for at least three days). The enoxacin levels in the alveolar film were extrapolated from the lavage content by using urea as an internal marker (lavage dilution factor = plasma/lavage urea concentration ratio). The concentration in the alveolar film amounted to 7.62 mg/l (=381% of the plasma value), on average, and exceeded the minimal inhibitory concentrations of the pathogens isolated from the patients. Thus, enoxacin is effectively concentrated in the surface film of the lung which represents an important barrier against pulmonary infections.
    Notes: Zusammenfassung Wir bestimmten Enoxacin-Spiegel in Plasma, Speichel, Bronchialsekret, Lavageflüssigkeit und Alveolarmakrophagen bei neun Patienten fünf Stunden nach der letzten Einnahme (2×400 mg Enoxacin täglich für mindestens drei Tage). Die Enoxacin-Konzentration im Alveolarfilm wurde mittels Harnstoff als internem Marker für die Lavage ermittelt. Sie betrug durchschnittlich 7,62 mg/l (=381% des Plasmaspiegels) und übertraf deutlich die minimalen Hemmkonzentrationen für die von den Patienten isolierten, fakultativ pathogenen Keime. Im Alveolarfilm als der Barriere für eine deszendierende Pneumonie kommt es somit zu einer effektiven Anreicherung des Chinolons.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01643631
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  • 9
    Electronic Resource
    Electronic Resource
    Enoxacin-konzentrationen im Knochengewebe (1989)
    Springer
    Infection 17 (1989), S. S25 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary For successful treatment of bacterial osteomyelitis the administered antibiotic must reach sufficiently high concentrations in bone tissues. Therefore concentrations of enoxacin in bone in ten patients requiring hip surgery were measured. To prevent a postoperative infection, 400 mg enoxacin b.i.d. for two days were administered. On an average 120 (90–210) min after the final dose samples of venous blood and bone tissue were taken. The bone pieces were divided into corticalis and spongiosa. Using a bio-assay-method the following concentrations were found: (mean ± S.D.): serum 2.88 (±0.90) mg/l, corticalis 5.90 (±0.79) mg/kg, spongiosa 3.95 (±1.01) mg/kg. Thus enoxacin reaches higher levels in bone tissue than in serum.
    Notes: Zusammenfassung Für die erfolgreiche Behandlung einer bakteriellen Osteomyelitis ist es erforderlich, daß das verwendete Antibiotikum genügend hohe Konzentrationen im Knochengewebe erreicht. In dieser Studie wurden die Knochenkonzentrationen von Enoxacin bei zehn Patienten ermittelt, bei welchen eine Totalendoprothese des Hüftgelenks durchgeführt wurde. Zur Prophylaxe einer postoperativen Infektion erhielten die Patienten zwei Tage lang 2×400 mg Enoxacin pro Tag. Durchschnittlich 120 (90–210) Minuten nach der letzten Gabe wurden venöse Blutproben und Knochenproben entnommen. Die Knochenstücke wurden in Corticalis und Spongiosa geteilt. Mit Hilfe eines Bioassay-Verfahrens wurden folgende Konzentrationen ermittelt (Mittelwert ± S.D.): Serum 2,88 (±0,90) mg/l, Corticalis 5,90 (±0,79) mg/kg, Spongiosa 3,95 (±1,01) mg/kg. Enoxacin erreicht also im Knochengewebe höhere Spiegel als im Serum.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01643632
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  • 10
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of teicoplanin in hemodialysis patients (1991)
    Springer
    Infection 19 (1991), S. 324-327 
    Details
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Da bisher nur unzureichende Daten über die Dosierung von Teicoplanin bei Hämodialysepatienten vorlagen, wurde eine Studie mit 26 Patienten durchgeführt. Die Patienten erhielten initial 800 mg Teicoplanin i.v. und dann jeweils 400 mg am 8. und 15. Tag. Neben den üblichen klinischen Parametern (Fieber, CRP, Leukocyten) wurden die Plasmaspiegel bestimmt. Die terminale Halbwertzeit betrug 159±35 h, das Verteilungsvolumen 104±25 l/100 kg und die totale Clearance 5,3±1,3 ml/min. Es zeigte sich, daß unter dieser Medikation lang- und hochwirksame Spiegel vorlagen, die weit über der minimalen Hemmkonzentration von Zielkeimen (Streptokokken und Staphylokokken) liegen. Die bequem zu applizierende Medikation wurde gut vertragen. Die Form der Behandlung führte nach klinischen Kriterien fast stets zum Erfolg. Aus diesen Gründen und wegen der einfachen Applikationsart erscheint es angebracht, bei Dialysepatienten, die offensichtlich an bakteriellen Infektionen erkrankt sind, die Therapie mit Teicoplanin einzuleiten.
    Notes: Summary As only insufficient knowledge about the dosage of teicoplanin in hemodialysis patients exists, a clinical trial was performed on 26 patients. An initial dose of 800 mg teicoplanin, followed by doses of 400 mg on day 8 and day 15, was administered. In addition to the common clinical parameters (fever, white blood cell count, C-reactive protein), the plasma concentrations of this substance were determined. The HLTterm was 159±35 h, the Vss 104±25 l/100 kg and the CLtot 5.3±1.3 ml/min. It could be shown that the dosage regimen mentioned above produced long-lasting and highly effective levels, sufficiently surpassing the MICs of the expected bacteria (streptococci and staphylococci). The easily administered substance showed no adverse side effects, based on clinical criteria. The above-mentioned therapy nearly always resulted in success according to clinical criteria. Therefore, and due to its easy administration, it seems advantageous to start treatment with teicoplanin in hemodialysis patients obviously suffering from bacterial infections.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01645356
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