Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Electronic Resource
    Electronic Resource
    Dose dependent methotrexate elimination following bolus intravenous injection (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 371-374 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; renal clearance ; nonlinear pharmacokinetics ; methotrexate-RIA ; patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of methotrexate have been assessed at two dose levels in six patients recciving the drug for treatment of malignant disease. Each patient received bolus intravenous doses of 25 mg and 100 mg given at least one week apart, the order of administration being random. Blood and urine were collected until 48 h for methotrexate analysis by radioimmunoassay and data analysed by a model-independent pharmacokinetic approach. In each patient area under the methotrexate serum concentration-time curve (o to ∞) increased out of proportion to the increase in methotrexate dose. This was reflected in a mean clearance value after the 100 mg dose of 31±16 (SD) ml · min−1 compared with a mean clearance of 62±19 ml · min−1 following injection of 25 mg methotrexate. Renal clearance of methotrexate was markedly lower following the 100 mg dose (18±6 ml · min−1) than after 25 mg (53±19 ml · min−1). Saturation of the proximal tubular organic acid transport system is the likely cause of methotrexate's capacity limited elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558450
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    The influence of protein binding on disopyramide clearance (1982)
    Springer
    European journal of clinical pharmacology 23 (1982), S. 453-456 
    Details
    ISSN: 1432-1041
    Keywords: disopyramide ; steady state ; clearance ; plasma protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Individual disopyramide clearance is not constant and previous studies have suggested that this may be time and/or concentration dependent. Steady state disopyramide concentrations were achieved in six volunteer subjects at each of three infusion rates. Drug analysis was by HPLC and protein binding was determined by ultrafiltration. The disopyramide free fraction was concentration dependent and marked interindividual variability was observed. Disopyramide clearance was independent of time but dependent on total plasma concentration. This can be completely explained by non-linear protein binding since free disopyramide clearance was observed to be independent of free concentration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00605997
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    The protein binding of methotrexate by the serum of normal subjects (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 363-366 
    Details
    ISSN: 1432-1041
    Keywords: methotrexate ; protein binding ; ultrafiltration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of methotrexate by serum from eight normal volunteers was assessed by continuous ultrafiltration at pH 7.4 and 37°C. Methotrexate concentrations were measured by radioimmunoassay and the data analysed by the method of Scatchard. The major binding protein was albumin which bound 87.3% of the drug in serum. Analysis of the Scatchard plots indicated two distinct groups of binding sites. Class I was found to have 0.16±0.05 (S D) binding sites with an intrinsic association constant of 71.15±35.98 (S D)×104 M−1: Class II had 2.01±0.93 (S D) binding sites and an affinity of 0.18±0.15×104 M−1. No great change in the percentage of methotrexate bound occurred until the total concentration of the drug exceeded 50 µMol 1−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558441
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    The protein binding of vinblastine in the serum of normal subjects and patients with Hodgkin's disease (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 683-687 
    Details
    ISSN: 1432-1041
    Keywords: vinblastine ; protein binding ; Hodgkin's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of vinblastine was measured in the serum from 6 normal subjects and 9 patients with Hodgkin's disease. Cellulose acetate electrophoresis showed that the predominant binding protein fractions were the α1- and α2-globulins with little binding to albumin and β- and γ-globulins. At a serum concentration of 10 nM a significantly lower percentage bound was found in the patient group (p=0.001). Binding to both groups was very high at 99.7% bound in the normal subjects and 98.9% bound in the patient group. Binding in both groups was best described by a two class protein binding model with higher and lower affinity binding sites. No significant difference was found on inter-group comparisons of binding parameter values.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542223
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Alterations of phenytoin protein binding with in vivo haemodialysis in dialysis encephalopathy (1979)
    Springer
    European journal of clinical pharmacology 15 (1979), S. 69-71 
    Details
    ISSN: 1432-1041
    Keywords: phenytoin ; dialysis encephalopathy ; protein binding ; continuous ultrafiltration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Protein binding of phenytoin was assessed in one patient with dialysis encephalopathy before and after haemodialysis. Phenytoin concentrations were measured by radioimmunoassay and continuous ultrafiltration was used to assess phenytoin binding. At a serum concentration of 60 µmol.1−1 the percentage of phenytoin bound to serum albumin was considerably lower in the patient serum (79.95% predialysis; 92.09% postdialysis) than that in three normal sera (97.90±0.17%). Analysis of Scatchard plots indicated two classes of binding sites. In class I both the affinity and capacity for binding phenytoin were reduced in the pre and post-dialysis serum, whereas in class II the capacity of the uraemic serum was increased although the intrinsic association constant was greatly reduced. It was concluded that in vivo haemodialysis is associated with large fluctuations in the protein binding of phenytoin, in which the concentration of endogenous dialysible metabolites are strongly implicated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563560
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 6
    Electronic Resource
    Electronic Resource
    Binding of vinblastine to recrystallized human α1-acid glycoprotein (1982)
    Springer
    Cancer chemotherapy and pharmacology 10 (1982), S. 40-42 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The binding of vinblastine (VLB) to recrystallized human α1-acid glycoprotein (α1-AGP) dissolved in phosphate-buffered saline (pH 7.4) was determined at different drug concentrations using the technique of continuous ultrafiltration. Vinblastine was extremely highly bound (〉99.0%) at a drug concentration of 4.0 μmol·l-1, dropping to under 60% at 65.0 μmol·l-1. Binding was best described by a two-class model with higher-(9.4 μM-1) and lower-(0.1 μM-1) affinity sites but with a similar number of binding sites (1.5 as against 1.1 lower-affinity sites). These results strongly suggest that α1-AGP would be a major binding protein for VLB in plasma.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00257236
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 7
    Electronic Resource
    Electronic Resource
    The protein binding of methotrexate in the serum of patients with neoplastic disease (1981)
    Springer
    Cancer chemotherapy and pharmacology 7 (1981), S. 61-64 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Serum protein binding of methotrexate was studied in 14 patients with various forms of malignant disease and in eight age- and sex-matched subjects (control group) attending outpatient clinics for various clinical conditions. 2. Protein binding was determined by continuous ultrafiltration and methotrexate concentrations by double-antibody radioimmunoassay. 3. Protein binding of the drug is critically dependent on albumin concentration, as shown by results in individual subjects and a significant regression of methotrexate binding on albumin concentration. Moreover, at high methotrexate concentrations drug binding becomes non-linear, resulting in disproportional elevation of free methotrexate levels. Both these findings have important implications for the treatment of hypoalbuminaemic patients. 4. Two classes of binding sites were observed in both groups of patients, viz a high-affinity, low-capacity group and a low-affinity group with higher capacity. 5. No significant difference was found between patient and control groups either in the percent bound drug or in the binding parameters. 6. In conclusion, while there appear to be no factors specific to malignant disease which perturb methotrexate's protein binding, it may be important to determine the extent of drug binding before methotrexate can be used judiciously, particularly when total drug level is related to likely toxicity and in the design of an appropriate folinic acid rescue regimen after high-dose therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00258215
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 8
    Electronic Resource
    Electronic Resource
    Enhancement of methotrexate absorption by subdivision of dose (1979)
    Springer
    Cancer chemotherapy and pharmacology 3 (1979), S. 235-237 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A comparison was made in fasting patients between a single 100 mg oral dose of methotrexate formulated as its sodium salt in a palatable syrup and the same total quantity of drug administered in four divided doses of 25 mg taken at 2-h intervals. Allocation to the order of these treatment schedules was on a random basis. The area under the serum methotrexate concentration-time curve until 50 h was found to be considerably greater after the divided dose regimen, the mean ratio AUC 25 mg x 4/AUC 100 mg being 1.86 (±0.90). There was no significant difference in peak serum methotrexate concentrations or methotrexate half-life estimates between the two regimens, however. The results of this study are consistent with saturation of an intestinal transport process when methotrexate is administered orally in a single large dose.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254737
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 9
    Electronic Resource
    Electronic Resource
    Bioavailability of methotrexate: Implications for clinical use (1979)
    Springer
    Cancer chemotherapy and pharmacology 3 (1979), S. 239-241 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The absorption of oral methotrexate in syrup form has been compared in six patients with that of an identical IV dose (50 mg/m2). There was variable absorption amongst the group with respect to maximum levels achieved and the time taken to reach those levels. The area under the time-concentration curve was always smaller when the drug was given orally than after IV administration. A total of 33 patients receiving methotrexate for a variety of tumour types were followed for response to treatment and toxicity. A significantly longer methotrexate half-life (t1/2) was found in nine partial responders (9.2±1.6 h) than in the nonresponders (3.8±0.7 h). Severe methotrexate toxicity was not seen, though occasional mucositis, conjunctivitis, and diarrhoea occurred in seven patients. The side effects could not be predicted from the dose, the bioavailability data, or the serum creatinine. Measurements of serum and urine methotrexate levels are useful in the assessment of absorption and bioavailability of the drug and the prediction of tumour response.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00254738
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 10
    Electronic Resource
    Electronic Resource
    The in vivo distribution of methotrexate between plasma and erythrocytes (1982)
    Springer
    Cancer chemotherapy and pharmacology 9 (1982), S. 110-113 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. The concentration of methotrexate in whole blood, plasma and erythrocytes was measured in three patients receiving 250 mg methotrexate by continuous intravenous infusion over 12 h for different malignant diseases. 2. Methotrexate was measured using a double-antibody radioimmunoassay which facilitated drug monitoring for 1–2 weeks. 3. The concentration of methotrexate in plasma was much higher than that in whole blood and erythrocytes during the period of infusion, but this profile was reversed during the elimination phase. 4. The concentration in erythrocytes fell rapidly immediately after the infusion ended, but thereafter, in contrast to plasma levels, methotrexate concentrations in erythrocytes did not appear to decay during the elimination phase. In one patient the concentration/time profiles differed between treatment days. On the first occasion, at the initiation of chemotherapy, erythrocytes progressively accumulated methotrexate in the elimination phase against an apparent concentration gradient. On the second occasion this progressive increase was not observed, but as in the other two patients, methotrexate levels in red cells remained many times higher than drug levels in plasma throughout the period of observation. 5. Folinic acid administration did not appear to influence the distribution of methotrexate between red cells and plasma. 6. It was concluded that while the distribution between plasma and erythrocytes was probably mediated by complex mechanisms, the results were consistent with the erythrocyte mass behaving as a slowly exchanging kinetic compartment. Accumulation and persistence of a drug such as methotrexate in red cells might be expected to promote resistance and perhaps influence the expression of toxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265389
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...