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  • 11
    Electronic Resource
    Electronic Resource
    Stereoselective plasma protein binding of ibuprofen enantiomers (1989)
    Springer
    European journal of clinical pharmacology 36 (1989), S. 283-290 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00558161
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  • 12
    Electronic Resource
    Electronic Resource
    Clinical pharmacokinetics of pancuronium bromide (1976)
    Springer
    European journal of clinical pharmacology 10 (1976), S. 367-372 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00565627
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  • 13
    Electronic Resource
    Electronic Resource
    Impaired cimetidine absorption due to antacids and metoclopramide (1981)
    Springer
    European journal of clinical pharmacology 20 (1981), S. 225-228 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; antacids ; metoclopramide ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hyroxyde containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P〈0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544602
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  • 14
    Electronic Resource
    Electronic Resource
    Lack of inhibition of tolbutamide hydroxylation by cimetidine in man (1986)
    Springer
    European journal of clinical pharmacology 31 (1986), S. 235-237 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; tolbutamide ; pharmacokinetic interaction ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have investigated the influence of cimetidine on the disposition of tolbutamide in 7 healthy subjects, who received 250 mg tolbutamide daily for 4 days followed by the concomitant intake of cimetidine 400 mg twice daily for a further 4 days. Cimetidine had no effect on the disposition of tolbutamide, including the unbound hydroxylation clearance rate (324 ml·min−1, tolbutamide alone; 316 ml·min−1, tolbutamide plus cimetidine). The total urinary recovery of carboxy- and hydroxy-tolbutamide metabolites was 85.7±20.3% of the dose when tolbutamide was given alone and 78.9±14.3% when given with cimetidine. This lack of a pharmacokinetic interaction suggests selectivity of cimetidine-induced inhibition of Phase I drug oxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606666
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  • 15
    Electronic Resource
    Electronic Resource
    Drug utilization review in a teaching hospital: experience with vancomycin (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 457-461 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00280936
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  • 16
    Electronic Resource
    Electronic Resource
    Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 127-131 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; tablets ; relative bioavailability ; intraindividual changes ; first-pass metabolism ; stable isotope technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Although the absorption of verapamil is almost complete after oral administration, its bioavailability is low due to extensive hepatic first-pass metabolism. Besides large interindividual differences in first-pass metabolism, pronounced day-to-day intraindividual variations in first-pass metabolism are observed, leading to erroneous results in relative bioavailability studies. Stable isotope techniques, which permit simultaneous administration of a solution and a tablet, can successfully be used to overcome these difficulties. The method has the advantage that two experiments can be carried out in a single test. Furthermore, the number of subjects required in bioavailability studies can be greatly reduced. Using this technique the bioavailability of verapamil tablets (Isoptin® 80) relative to a stable labelled solution of verapamil was found to be 108.1%, with a 95% confidence interval between 89.1 and 127.1%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568399
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  • 17
    Electronic Resource
    Electronic Resource
    Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 133-137 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; bioavailability ; hepatic first-pass metabolism ; stable isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following i. v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 l/min) approached liver blood flow (1.5 l/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568400
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  • 18
    Electronic Resource
    Electronic Resource
    The effect of renal failure on the disposition and neuromuscular blocking action of pancuronium bromide (1977)
    Springer
    European journal of clinical pharmacology 12 (1977), S. 23-29 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00561401
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  • 19
    Electronic Resource
    Electronic Resource
    Influence of phenobarbital treatment on cimetidine kinetics (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; phenobarbital ; gastro-intestinal absorption ; bioavailability ; renal clearance ; non-renal clearance ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P〈0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544584
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  • 20
    Electronic Resource
    Electronic Resource
    Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 379-382 
    Details
    ISSN: 1432-1041
    Keywords: Codeine ; paracetamol ; codeine-6-glucuronide ; pharmacokinetics ; metabolism ; partial clearance ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (μmol·l−1·h) and CLR (ml·min−1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml·min−1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucoronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314972
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