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  • pharmacokinetics  (98)
  • phosphorus  (33)
  • Conference proceedings  (31)
  • Springer  (162)
  • 2000-2004  (8)
  • 1990-1994  (154)
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  • 1
    ISSN: 1432-1041
    Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0646
    Keywords: menogaril ; phase I ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-five patients with advanced refractory cancer were enrolled on this phase I study of menogaril administered orally every 4 weeks at dosages ranging from 85 mg/m2 to 625 mg/m2. An additional 12 patients received alternating oral and IV doses of menogaril (250 mg/m2 IV; 250–500 mg/m2 oral) with accompanying blood and urine sampling for pharmacokinetics analysis. Nausea and vomiting were the dose-limiting toxicities at the 625 mg/m2 dosage level; vomiting was inadequately relieved by prophylactic antiemetics at this dosage level. Other toxicities included sporadic leukopenia at all dosage levels; at dosages of 500 mg/m2 and 625 mg/m2, leukopenia 〈 3000/μl occurred in 7 of 24 patients. Anemia and thrombocytopenia were much less frequent toxicities. Among the patients receiving IV menogaril, peripheral vein phlebitis, leukopenia and anemia were the predominant toxicities. No antitumor responses were observed, yet one patient with nonsmall cell lung cancer experienced a 30% reduction in metastatic tumor nodules. For the patients receiving alternating oral and IV menogaril, comparative pharmacokinetic analyses were performed by HPLC. After oral administration, maximum plasma concentrations were achieved in an average of 6 hours; maximum plasma concentrations were less than one-quarter of those achieved after intravenous administration. The harmonic mean (±SD) terminal disposition half-life after oral dosing was 29.3 ±9.2 hours; mean systemic bioavailability was 33.6±10.5% after oral dosing. Forty-eight hours after an oral dose, mean cumulative urinary excretions of menogaril and the primary metabolite, N-demethylmenogaril, were 4.00±0.96% and 0.44±0.16%, respectively. Because of the poor tolerance of oral menogaril and minimal evidence of biological activity, this schedule of drug administration is not recommended for phase II evaluation. Based on this and other published studies of oral menogaril, frequent chronic low-intermediate dosages of the drug may be given orally with potentially better tolerance and antitumor activity.
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  • 3
    ISSN: 1573-904X
    Keywords: fibrinogen receptor antagonist ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of L-703,014, a fibrinogen receptor antagonist, have been examined in the dog. An analytical method which utilizes methanol precipitation of dog plasma proteins followed by HPLC with an automated column switching technique using the chemical analogue L-704,326 as internal standard was developed for the determination of L-703,014 in dog plasma. The compound was not metabolized in the dog and was eliminated in the kidneys and into bile. Of the administered dose, 68.9 ± 1.3% (i.v.) and 80.5 ± 11.9% (p.o.) were recovered in the feces; 20.3 ± 3% (i.v.) and 2.2 ± 0.2% (p.o.) were recovered in the urine by 72 hr. L-703,014 was 23 ± 3.4% bound in dog plasma protein and the mean ratio of plasma/whole blood was 1.22 ± 0.05. The mean terminal half-life was 118 ± 36 min, the mean steady-state volume of distribution was 0.61 ± 0.22 L/kg, and the mean plasma clearance was 8 ± 2 mL/min/kg. Ex vivo platelet aggregation measurements were made by inducing platelet aggregation with 10 µg/ mL collagen in the presence of 1 µM epinephrine as an agonist. The mean C 50 was 44.4 ± 6.0 ng/mL, and the mean Hill coefficient was 1.5 ± 0.3. The mean bioavailability was 4.9 ± 1.4% in dogs administered 2.0 mg/kg (p.o.).
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Il nuovo cimento della Società Italiana di Fisica 16 (1994), S. 1619-1625 
    ISSN: 0392-6737
    Keywords: Brillouin and Rayleigh scattering ; Ultrasonic relaxation processes in gases, liquids, and solids ; Acoustical properties of liquids ; Order-disorder and statistical mechanics of model systems ; Conference proceedings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary A water/butoxyethanol solution has been investigated by means of several techniques (viscosity, ultrasound and hypersound) as a function of concentration and temperature. The butoxyethanol molar fraction range investigated was situated between 0.015 and 0.09, while temperature ranged between −10°C and +45°C. We observed the building-up of large structures lowering the temperature, in particular below +15°C. All data coming from different techniques seem to confirm such a picture and indicate that this aggregation phenomenon is a percolation-like process.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Il nuovo cimento della Società Italiana di Fisica 16 (1994), S. 747-755 
    ISSN: 0392-6737
    Keywords: Neutron scattering techniques (including small-angle scattering) ; Polymers, elastomers, and plastics ; Fluctuation phenomena, random processes and Brownian motion ; Conference proceedings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary A-B block copolymers in a selective solvent—good for the B-species and bad for the A-species—form micellar aggregates with a compact A-core with a corona (brush) of B «hairs» reaching into the solvent. Whereas polystyrene(PS)-polyisoprene(PI) in decane forms spherical micelles with a PS core of about 10 nm radius, polyethylene(PE)-polyethylenepropylene(PEP) forms micellar platelets, the shape of which is goverend by the habitus of PE crystallites forming the core. These planar aggregates have large (several hundred nanometers) lateral extension and a core thickness in the range of 10 nm. Both systems are model systems for polymer brushes, either on a spherical surface or planar. Neutron spin-echo experiments allow for the investigation of the dynamics of the brushes which reflects their viscoelastic properties. Results of neutron small-angle and spin-echo investigations are reported. The brush dynamics is explained using a model based on an idea of de Gennes describing the brush properties in terms of scaling relations for osmotic pressure and viscosity of a semi-dilute solution with inhomogeneous density.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Il nuovo cimento della Società Italiana di Fisica 16 (1994), S. 1357-1366 
    ISSN: 0392-6737
    Keywords: Fluid surfaces and fluid-fluid interfaces ; Neutron scattering techniques (including small-angle scattering) ; Conference proceedings
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Summary Water-octane-C10E4 microemulsions in both the isotropic and lamellar phases were measured using small-angle neutron scattering. Varying the scattering length density of both the water and oil through hydrogen-deuterium substitution enabled us to isolate the scattering contributions of the surfactant monolayers and the water-surfactant and oil-surfactant interfaces. Analyses of the resulting scattering patterns allow us to directly determine the small mean curvature of the surfactant film as a function of temperature and correlate this quantity with the overall phase behavior. A simulation using a Gaussian random field yields the three-dimensional structure of the bicontinuous microemulsion having a surfactant monolayer with zero mean curvature.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 559-560 
    ISSN: 1432-1041
    Keywords: Mefloquine ; Thai subjects ; pharmacokinetics ; Primaquine ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 40 (1991), S. 631-633 
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
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  • 9
    ISSN: 1432-1041
    Keywords: Halofantrine ; Malaria falciparum ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Halofantrine is a new blood schizontocidal drug used for the treatment of multidrug-resistant falciparum malaria. The pharmacokinetics of halofantrine (HAL) and its principal metabolite, N-desbutylhalofantrine (BHAL), was investigated in 6 adult male patients of Melanesian origin with uncomplicated falciparum malaria. The patients received 500 mg of halofantrine hydrochloride at times 0, 6 and 12 h (total 1.5 g). All patients responded to treatment with a mean parasite clearance time of 52.7 h and a mean fever clearance time of 33.8 h. The following kinetic parameters (mean values) were determined for HAL and BHAL, respectively: maximum plasma concentration (Cmax)=896 and 491 ng·ml−1; time to reach the Cmax (tmax)=15 and 56 h; elimination half-life (t1/2)=91 and 79 h and the mean residence time (MRT)=71 and 102 h. Based on the clinical response the plasma concentrations of HAL and BHAL were adequate for the treatment of uncomplicated falciparum malaria in the 6 patients.
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  • 10
    ISSN: 1432-1041
    Keywords: Fosinopril ; fosinoprilat ; CAPD ; ACE-inhibitor ; pharmacokinetics ; pharmacodynamics ; peritoneal dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium, a new angiotensin-converting enzyme (ACE) inhibitor, were investigated after the oral administration of 10 mg of fosinopril sodium to 6 chronic ambulatory peritoneal dialysis (CAPD) patients. The results from 1 patient are reported separately because of the presence of concomitant liver dysfunction. The mean t1/2, Cmax, tmax, and AUC values for 5 of the CAPD patients were 19.5 h, 202 ng·ml−1, 4.8 h, and 3.19 μg·h·ml−1, respectively. Values for 1 CAPD patient with liver dysfunction were t1/2 of 65.4 h, Cmax of 182 ng·ml−1, tmax of 9 h, and AUC of 18.1 μg·h·ml−1. Peritoneal clearance of fosinoprilat was negligible, ranging from 0.07 to 0.23 ml·min−1. Serum ACE activity remained significantly suppressed at 24 and 48 h after fosinopril sodium administration with mean decreases from baseline of 94.2% and 70.6%, respectively. ACE activity was suppressed to an even greater degree in the patient with liver dysfunction, remaining 97% inhibited 72 h after drug administration. Plasma renin activity (PRA) increased and plasma aldosterone concentrations decreased following drug administration. Mean arterial pressure did not change appreciably throughout the study. Dosage reductions may not be necessary in the majority of dialysis patients.
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