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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    ISSN: 1432-1041
    Keywords: ibuprofen ; enantiomers ; stereoselective protein binding ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have developed a novel and reproducible method for determining the plasma protein binding of the two ibuprofen enantiomers in the presence of each other. The method involves the use of radiolabelled racemic ibuprofen, equilibrium dialysis, derivatization of the enantiomers to diastereomeric amides, high-performance liquid chromatography, and radiochemical analysis. We have determined the plasma protein binding of R(−)- and S(+)-ibuprofen in 6 healthy male volunteers after the oral administration of 800 mg racemic ibuprofen. The mean time-averaged percentage unbound of the R(−)-enantiomer, 0.419 was significantly less than that of the S(+)-enantiomer, 0.643, consistent with stereoselective plasma protein binding. The percentage unbound of each ibuprofen enantiomer was concentration-dependent over the therapeutic concentration range and was influenced by the presence of its optical antipode.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 10 (1976), S. 367-372 
    ISSN: 1432-1041
    Keywords: Pharmacokinetics ; pancuronium ; neuro-muscular blockade
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of pancuronium bromide have been studied in seven surgical patients following a 6 mg intravenous bolus injection of the drug for neuromuscular blockade. Concurrently, evoked muscle twitch response was monitored for each patient as a measure of the pharmacodynamic effect of the drug. The plasma decay curve for pancuronium was found to be biphasic and after rigorous statistical analysis the data were interpreted according to a 2-compartment open model. The half-life of the β-phase varied between 89.5 and 161.5 min. The apparent volume of distribution of the central compartment ranged from 62.9 to 145.5 ml/kg and the plasma clearance from 57.6 to 187.3 ml/min. At the first sign of recovery from neuro-muscular blockade the mean pancuronium plasma level was found to be 0.218 mcg/ml. The mean duration of action as measured from time of onset of paralysis to 20% recovery was 83.4 min with the plasma level at 20% being 0.169 mcg/ml corresponding to 45.4% of dose remaining to be eliminated from the body.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 457-461 
    ISSN: 1432-1041
    Keywords: Vancomycin ; drug utilization ; drug usage evaluation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A prospective, two-phase, drug utilization review (DUR) was performed at the Royal Adelaide Hospital (RAH) to determine the extent and pattern of vancomycin use. For all patients commencing oral or parenteral vancomycin, treatment indication, route of administration, duration of therapy, results of culture and sensitivity tests, adverse drug reactions and results of therapeutic drug level monitoring were recorded. Vancomycin courses were classified as being for therapy or prophylaxis and compared with predetermined audit criteria to assess appropriateness of use. During the 8 week initial phase, data on 62 treatment courses in 59 patients were recorded, 50% for therapy and 50% for prophylaxis. Sixty four percent were classified as inappropriate, occurring in 32% of therapeutic courses and 97% of those for prophylaxis. During the 10 week re-evaluation, conducted 10 months later, data for 43 treatment courses in 43 patients were reviewed, 42% for therapy and 58% for prophylaxis. Sixty five percent were inappropriate occuring in 17% of therapeutic courses and 100% of the prophylactic courses. When compared with the initial phase, the re-evaluation demonstrated a decrease in the empirical use of vancomycin in the combination treatment of neutropaenic fever and also in the duration of vancomycin use for surgical prophylaxis. During both study phases, criteria contraventions were mostly due to inappropriate indication or duration of therapy. The cost of inappropriate vancomycin use was reduced by over 50% between survey phases, from $Aus11,500 or 55% of total vancomycin cost during the initial phase to $Aus3,600 or 25.7% during the re-evaluation. The most effective of the remedial strategies implemented after the initial phase was direct consultation with prescriber groups. The effectiveness of this DUR has provided the basis for an ongoing DUR programme at the RAH which has been met with general acceptance by hospital clinicians and administrators.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 12 (1977), S. 23-29 
    ISSN: 1432-1041
    Keywords: Pancuronium ; renal transplant ; single and multiple dosing ; plasma levels and twitch response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma concentrations of pancuronium following single dose administration in six patients, and following multiple dose administration in four patients, all undergoing renal transplantation surgery, were measured using a fluorimetric method. A two-compartment open model was used in the pharmacokinetic analysis of the data. Comparison of the pharmacokinetic findings with data previously obtained for patients undergoing elective surgery but having normal renal function indicated that the clearance of the drug was reduced significantly in the patients with renal failure, and that in these individuals the half-life was increased significantly. Measurement of the evoked mechanical twitch response concurrently with plasma concentration monitoring of pancuronium confirmed that the prolongation of half-life in the patients with renal failure was often but not always associated with an extended duration of neuromuscular blockade and furthermore that the rate of recovery from block might also be prolonged. The clinical implications of these findings are discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 50 (1996), S. 417-419 
    ISSN: 1432-1041
    Keywords: Key words Proguanil ; Omeprazole ; Cimetidine; druginteraction ; metabolic ratio ; CYP2C19
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To examine the effects of omeprazole and cimetidine on the urinary recovery and metabolic ratio of proguanil in healthy subjects. Methods: A metabolic interaction study was conducted in 12 young, healthy extensive metabolisers of proguanil, a CYP2C19 substrate, following a single 100 mg oral dose by analysis of urine collected for 8 hours. Results: Concomitant administration of omeprazole (20 mg), a CYP2C19 substrate, had no significant effect on the urinary recovery of proguanil or cycloguanil, or the ratio of cycloguanil to proguanil [mean 0.76 (95% CI: 0.53 to 0.98) proguanil alone; mean 0.65 (95% CI: 0.40 to 0.89) proguanil plus omeprazole]. In contrast, cimetidine (400 mg), a general CYP inhibitor and renal organic cation secretion inhibitor, decreased the urinary recovery of cycloguanil and reduced the metabolic ratio from a mean of 0.76 to 0.54 (P 〈 0.01). In 3 poor metabolisers of proguanil, cimetidine had no effect on the proguanil metabolic ratio. Conclusion: The concomitant administration of omeprazole or cimetidine will not result in phenocopying extensive metabolisers of proguanil, although cimetidine inhibits the formation of cycloguanil in extensive metabolisers.
    Type of Medium: Electronic Resource
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